The Neuropathology of Huntington’s Disease

  • Henry J. WaldvogelEmail author
  • Eric H. Kim
  • Lynette J. Tippett
  • Jean-Paul G. Vonsattel
  • Richard LM Faull
Part of the Current Topics in Behavioral Neurosciences book series (CTBN, volume 22)


The basal ganglia are a highly interconnected set of subcortical nuclei and major atrophy in one or more regions may have major effects on other regions of the brain. Therefore, the striatum which is preferentially degenerated and receives projections from the entire cortex also affects the regions to which it targets, especially the globus pallidus and substantia nigra pars reticulata. Additionally, the cerebral cortex is itself severely affected as are many other regions of the brain, especially in more advanced cases. The cell loss in the basal ganglia and the cerebral cortex is extensive. The most important new findings in Huntington’s disease pathology is the highly variable nature of the degeneration in the brain. Most interestingly, this variable pattern of pathology appears to reflect the highly variable symptomatology of cases with Huntington’s disease even among cases possessing the same number of CAG repeats.


Human brain Neuropathology Neurochemical Striosomes Basal ganglia Striatum Globus pallidus Symptomatology 


  1. Albin RL, Reiner A, Anderson KD, Dure LS, Handelin B, Balfour R, Whetsell WO Jr, Penney JB, Young AB (1992) Preferential loss of striato-external pallidal projection neurons in presymptomatic Huntington’s disease. Ann Neurol 31(4):425–430PubMedGoogle Scholar
  2. Albin RL, Reiner A, Anderson KD, Penney JB, Young AB (1990) Striatal and nigral neuron subpopulations in rigid Huntington’s disease: implications for the functional anatomy of chorea and rigidity-akinesia. Ann Neurol 27(4):357–365PubMedGoogle Scholar
  3. Albin RL, Young AB, Penney JB (1989) The functional anatomy of basal ganglia disorders. Trends Neurosci 12(10):366–375PubMedGoogle Scholar
  4. Alexander GE, Crutcher MD (1990) Functional architecture of basal ganglia circuits: neural substrates of parallel processing. Trends Neurosci 13(7):266–271PubMedGoogle Scholar
  5. Allen KL, Waldvogel HJ, Glass M, Faull RLM (2009) Cannabinoid (CB(1)), GABA(A) and GABA(B) receptor subunit changes in the globus pallidus in Huntington’s disease. J Chem Neuroanat 37(4):266–281PubMedGoogle Scholar
  6. Andre VM, Cepeda C, Venegas A, Gomez Y, Levine MS (2006) Altered cortical glutamate receptor function in the R6/2 model of Huntington’s disease. J Neurophysiol 95(4):2108–2119PubMedGoogle Scholar
  7. Andreassen OA, Dedeoglu A, Stanojevic V, Hughes DB, Browne SE, Leech CA, Ferrante RJ, Habener JF, Beal MF, Thomas MK (2002) Huntington’s disease of the endocrine pancreas: insulin deficiency and diabetes mellitus due to impaired insulin gene expression. Neurobiol Dis 11(3):410–424PubMedGoogle Scholar
  8. Andrew SE, Goldberg YP, Kremer B, Telenius H, Theilmann J, Adam S, Starr E, Squitieri F, Lin B, Kalchman MA et al (1993) The relationship between trinucleotide (CAG) repeat length and clinical features of Huntington’s disease. Nat Genet 4(4):398–403PubMedGoogle Scholar
  9. Arenas J, Campos Y, Ribacoba R, Martin MA, Rubio JC, Ablanedo P, Cabello A (1998) Complex I defect in muscle from patients with Huntington’s disease. Ann Neurol 43(3):397–400PubMedGoogle Scholar
  10. Aronin N, Chase K, Young C, Sapp E, Schwarz C, Matta N, Kornreich R, Landwehrmeyer B, Bird E, Beal MF et al (1995) CAG expansion affects the expression of mutant Huntingtin in the Huntington’s disease brain. Neuron 15(5):1193–1201PubMedGoogle Scholar
  11. Arrasate M, Mitra S, Schweitzer ES, Segal MR, Finkbeiner S (2004) Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death. Nature 431(7010):805–810PubMedGoogle Scholar
  12. Atwal RS, Xia J, Pinchev D, Taylor J, Epand RM, Truant R (2007) Huntingtin has a membrane association signal that can modulate huntingtin aggregation, nuclear entry and toxicity. Hum Mol Genet 16(21):2600–2615PubMedGoogle Scholar
  13. Augood SJ, Faull RLM, Love DR, Emson PC (1996) Reduction in enkephalin and substance P messenger RNA in the striatum of early grade Huntington’s disease: a detailed cellular in situ hybridization study. Neuroscience 72(4):1023–1036PubMedGoogle Scholar
  14. Aylward EH, Anderson NB, Bylsma FW, Wagster MV, Barta PE, Sherr M, Feeney J, Davis A, Rosenblatt A, Pearlson GD, Ross CA (1998) Frontal lobe volume in patients with Huntington’s disease. Neurology 50(1):252–258PubMedGoogle Scholar
  15. Aylward EH, Li Q, Stine OC, Ranen N, Sherr M, Barta PE, Bylsma FW, Pearlson GD, Ross CA (1997) Longitudinal change in basal ganglia volume in patients with Huntington’s disease. Neurology 48(2):394–399PubMedGoogle Scholar
  16. Aylward EH, Sparks BF, Field KM, Yallapragada V, Shpritz BD, Rosenblatt A, Brandt J, Gourley LM, Liang K, Zhou H, Margolis RL, Ross CA (2004) Onset and rate of striatal atrophy in preclinical Huntington disease. Neurology 63(1):66–72PubMedGoogle Scholar
  17. Aziz A, Fronczek R, Maat-Schieman M, Unmehopa U, Roelandse F, Overeem S, van Duinen S, Lammers GJ, Swaab D, Roos R (2008) Hypocretin and melanin-concentrating hormone in patients with Huntington disease. Brain Pathol 18(4):474–483PubMedGoogle Scholar
  18. Beal MF (1994) Huntington’s disease, energy, and excitotoxicity. Neurobiol Aging 15(2):275–276PubMedGoogle Scholar
  19. Becher MW, Kotzuk JA, Sharp AH, Davies SW, Bates GP, Price DL, Ross CA (1998) Intranuclear neuronal inclusions in Huntington’s disease and dentatorubral and pallidoluysian atrophy: correlation between the density of inclusions and IT15 CAG triplet repeat length. Neurobiol Dis 4(6):387–397PubMedGoogle Scholar
  20. Bevan MD, Booth PA, Eaton SA, Bolam JP (1998) Selective innervation of neostriatal interneurons by a subclass of neuron in the globus pallidus of the rat. J Neurosci 18(22):9438–9452PubMedGoogle Scholar
  21. Bhatia KP, Marsden CD (1994) The behavioural and motor consequences of focal lesions of the basal ganglia in man. Brain 117(Pt 4):859–876PubMedGoogle Scholar
  22. Bird ED, Iversen LL (1974) Huntington’s chorea. Post-mortem measurement of glutamic acid decarboxylase, choline acetyltransferase and dopamine in basal ganglia. Brain 97(3):457–472PubMedGoogle Scholar
  23. Birnbaum G (1941) Chronisch-progressive Chorea mit Kleinhirnatrophie. Archiv für Psychiatrie und Nervenkrankheiten 114:160–182Google Scholar
  24. Bohanna I, Georgiou-Karistianis N, Hannan AJ, Egan GF (2008) Magnetic resonance imaging as an approach towards identifying neuropathological biomarkers for Huntington’s disease. Brain Res Rev 58(1):209–225PubMedGoogle Scholar
  25. Brandt J, Butters N (1986) The neuropsychology of Huntington’s disease. Trends Neurosci 9:118–120Google Scholar
  26. Bryun GW (1968) Huntington’s chorea; historical, clinical and laboratory synopsis. In: Vinken PJ, Bruyn GW (eds) Handbook of clinical neurology, vol 6. North Holland, Amsterdam, pp 379–396Google Scholar
  27. Byers RK, Gilles FH, Fung C (1973) Huntington’s disease in children. Neuropathologic study of four cases. Neurology 23(6):561–569Google Scholar
  28. Campbell AM, Corner B, Norman RM, Urich H (1961) The rigid form of Huntington’s disease. J Neurol Neurosurg Psychiatry 24:71–77PubMedCentralPubMedGoogle Scholar
  29. Carpenter MB, Nakano K, Kim R (1976) Nigrothalamic projections in the monkey demonstrated by autoradiographic technics. J Comp Neurol 165(4):401–415PubMedGoogle Scholar
  30. Cattaneo E, Rigamonti D, Goffredo D, Zuccato C, Squitieri F, Sipione S (2001) Loss of normal huntingtin function: new developments in Huntington’s disease research. Trends Neurosci 24(3):182–188PubMedGoogle Scholar
  31. Cepeda C, Wu N, Andre VM, Cummings DM, Levine MS (2007) The corticostriatal pathway in Huntington’s disease. Prog Neurobiol 81(5–6):253–271PubMedCentralPubMedGoogle Scholar
  32. Cha JH (2000) Transcriptional dysregulation in Huntington’s disease. Trends Neurosci 23(9):387–392PubMedGoogle Scholar
  33. Cicchetti F, Parent A (1996) Striatal interneurons in Huntington’s disease: selective increase in the density of calretinin-immunoreactive medium-sized neurons. Mov Disord 11(6):619–626PubMedGoogle Scholar
  34. Cicchetti F, Prensa L, Wu Y, Parent A (2000) Chemical anatomy of striatal interneurons in normal individuals and in patients with Huntington’s disease. Brain Res Brain Res Rev 34(1–2):80–101PubMedGoogle Scholar
  35. Claes S, Van Zand K, Legius E, Dom R, Malfroid M, Baro F, Godderis J, Cassiman JJ (1995) Correlations between triplet repeat expansion and clinical features in Huntington’s disease. Arch Neurol 52(8):749–753PubMedGoogle Scholar
  36. Cudkowicz M, Kowall NW (1990a) Degeneration of pyramidal projection neurons in Huntington’s disease cortex. Ann Neurol 27(2):200–204PubMedGoogle Scholar
  37. Cudkowicz M, Kowall NW (1990b) Parvalbumin immunoreactive neurons are resistant to degeneration in Huntington’s disease cerebral cortex. J Neuropathol Exp Neurol 49:345Google Scholar
  38. Cummings DM, Andre VM, Uzgil BO, Gee SM, Fisher YE, Cepeda C, Levine MS (2009) Alterations in cortical excitation and inhibition in genetic mouse models of Huntington’s disease. J Neurosci 29(33):10371–10386PubMedCentralPubMedGoogle Scholar
  39. Curtis MA, Kam M, Nannmark U, Anderson MF, Axell MZ, Wikkelso C, Holtas S, van Roon-Mom WM, Bjork-Eriksson T, Nordborg C, Frisen J, Dragunow M, Faull RLM, Eriksson PS (2007) Human neuroblasts migrate to the olfactory bulb via a lateral ventricular extension. Science 315(5816):1243–1249PubMedGoogle Scholar
  40. Curtis MA, Low VF, Faull RLM (2012) Neurogenesis and progenitor cells in the adult human brain: a comparison between hippocampal and subventricular progenitor proliferation. Dev Neurobiol 72(7):990–1005PubMedGoogle Scholar
  41. Curtis MA, Penney EB, Pearson AG, van Roon-Mom WM, Butterworth NJ, Dragunow M, Connor B, Faull RLM (2003) Increased cell proliferation and neurogenesis in the adult human Huntington’s disease brain. Proc Natl Acad Sci U S A 100(15):9023–9027PubMedCentralPubMedGoogle Scholar
  42. Curtis MA, Penney EB, Pearson J, Dragunow M, Connor B, Faull RLM (2005) The distribution of progenitor cells in the subependymal layer of the lateral ventricle in the normal and Huntington’s disease human brain. Neuroscience 132(3):777–788PubMedGoogle Scholar
  43. Davies SW, Turmaine M, Cozens BA, DiFiglia M, Sharp AH, Ross CA, Scherzinger E, Wanker EE, Mangiarini L, Bates GP (1997) Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell 90(3):537–548PubMedGoogle Scholar
  44. Davies SW, Turmaine M, Cozens BA, Raza AS, Mahal A, Mangiarini L, Bates GP (1999) From neuronal inclusions to neurodegeneration: neuropathological investigation of a transgenic mouse model of Huntington’s disease. Philos Trans R Soc Lond B Biol Sci 354(1386):981–989Google Scholar
  45. Dawbarn D, De Quidt ME, Emson PC (1985) Survival of basal ganglia neuropeptide Y-somatostatin neurones in Huntington’s disease. Brain Res 340(2):251–260PubMedGoogle Scholar
  46. de la Monte SM, Vonsattel JP, Richardson EP Jr (1988) Morphometric demonstration of atrophic changes in the cerebral cortex, white matter, and neostriatum in Huntington’s disease. J Neuropathol Exp Neurol 47(5):516–525PubMedGoogle Scholar
  47. DeLong MR (1990) Primate models of movement disorders of basal ganglia origin. Trends Neurosci 13(7):281–285PubMedGoogle Scholar
  48. Deng YP, Albin RL, Penney JB, Young AB, Anderson KD, Reiner A (2004) Differential loss of striatal projection systems in Huntington’s disease: a quantitative immunohistochemical study. J Chem Neuroanat 27(3):143–164PubMedGoogle Scholar
  49. Deng YP, Wong T, Bricker-Anthony C, Deng B, Reiner A (2013) Loss of corticostriatal and thalamostriatal synaptic terminals precedes striatal projection neuron pathology in heterozygous Q140 Huntington’s disease mice. Neurobiol Dis 60:89–107PubMedGoogle Scholar
  50. Di Maio L, Squitieri F, Napolitano G, Campanella G, Trofatter JA, Conneally PM (1993) Onset symptoms in 510 patients with Huntington’s disease. J Med Genet 30(4):289–292PubMedCentralPubMedGoogle Scholar
  51. DiFiglia M, Sapp E, Chase K, Schwarz C, Meloni A, Young C, Martin E, Vonsattel JP, Carraway R, Reeves SA et al (1995) Huntingtin is a cytoplasmic protein associated with vesicles in human and rat brain neurons. Neuron 14(5):1075–1081PubMedGoogle Scholar
  52. DiFiglia M, Sapp E, Chase KO, Davies SW, Bates GP, Vonsattel JP, Aronin N (1997) Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science 277(5334):1990–1993PubMedGoogle Scholar
  53. Doig NM, Moss J, Bolam JP (2010) Cortical and thalamic innervation of direct and indirect pathway medium-sized spiny neurons in mouse striatum. J Neurosci 30(44):14610–14618PubMedGoogle Scholar
  54. Douaud G, Gaura V, Ribeiro MJ, Lethimonnier F, Maroy R, Verny C, Krystkowiak P, Damier P, Bachoud-Levi AC, Hantraye P, Remy P (2006) Distribution of grey matter atrophy in Huntington’s disease patients: a combined ROI-based and voxel-based morphometric study. Neuroimage 32(4):1562–1575PubMedGoogle Scholar
  55. Dunlap CB (1927) Pathologic changes in Huntington’s chorea with special reference to the corpus striatum. Arch Neurol Psychiat 18:867–943Google Scholar
  56. Dure LS, Young AB, Penney JB (1991) Excitatory amino acid binding sites in the caudate nucleus and frontal cortex of Huntington’s disease. Ann Neurol 30 (6):785–793Google Scholar
  57. Dure LS, Young AB, Penney JB, Jr. (1992) Compartmentalization of excitatory amino acid receptors in human striatum. Proc Natl Acad Sci U S A 89 (16):7688–7692Google Scholar
  58. Duyao MP, Auerbach AB, Ryan A, Persichetti F, Barnes GT, McNeil SM, Ge P, Vonsattel JP, Gusella JF, Joyner AL et al (1995) Inactivation of the mouse Huntington’s disease gene homolog Hdh. Science 269(5222):407–410PubMedGoogle Scholar
  59. Emson PC, Arregui A, Clement-Jones V, Sandberg BE, Rossor M (1980) Regional distribution of methionine-enkephalin and substance P-like immunoreactivity in normal human brain and in Huntington’s disease. Brain Res 199(1):147–160PubMedGoogle Scholar
  60. Eriksson PS, Perfilieva E, Bjork-Eriksson T, Alborn AM, Nordborg C, Peterson DA, Gage FH (1998) Neurogenesis in the adult human hippocampus. Nat Med 4(11):1313–1317PubMedGoogle Scholar
  61. Faull RLM, Mehler WR (1978) The cells of origin of nigrotectal, nigrothalamic and nigrostriatal projections in the rat. Neuroscience 3(11):989–1002PubMedGoogle Scholar
  62. Faull RLM, Villiger JW (1986) Heterogeneous distribution of benzodiazepine receptors in the human striatum: a quantitative autoradiographic study comparing the pattern of receptor labelling with the distribution of acetylcholinesterase staining. Brain Res 381(1):153–158PubMedGoogle Scholar
  63. Faull RLM, Waldvogel HJ, Nicholson LF, Synek BJ (1993) The distribution of GABAA-benzodiazepine receptors in the basal ganglia in Huntington’s disease and in the quinolinic acid-lesioned rat. Prog Brain Res 99:105–123PubMedGoogle Scholar
  64. Ferrante RJ, Gutekunst CA, Persichetti F, McNeil SM, Kowall NW, Gusella JF, MacDonald ME, Beal MF, Hersch SM (1997) Heterogeneous topographic and cellular distribution of huntingtin expression in the normal human neostriatum. J Neurosci 17(9):3052–3063PubMedGoogle Scholar
  65. Ferrante RJ, Kowall NW (1987) Tyrosine hydroxylase-like immunoreactivity is distributed in the matrix compartment of normal human and Huntington’s disease striatum. Brain Res 416(1):141–146PubMedGoogle Scholar
  66. Ferrante RJ, Kowall NW, Beal MF, Martin JB, Bird ED, Richardson EP Jr (1987) Morphologic and histochemical characteristics of a spared subset of striatal neurons in Huntington’s disease. J Neuropathol Exp Neurol 46(1):12–27PubMedGoogle Scholar
  67. Ferrante RJ, Kowall NW, Richardson EP Jr (1989) Neuronal and neuropil loss in the substantia nigra in Huntington’s disease. J Neuropath Exp Neurol 48:380Google Scholar
  68. Ferrante RJ, Kowall NW, Richardson EP Jr (1991) Proliferative and degenerative changes in striatal spiny neurons in Huntington’s disease: a combined study using the section-Golgi method and calbindin D28k immunocytochemistry. J Neurosci 11(12):3877–3887PubMedGoogle Scholar
  69. Ferrer I, Kulisevsky J, Gonzalez G, Escartin A, Chivite A, Casas R (1994) Parvalbumin-immunoreactive neurons in the cerebral cortex and striatum in Huntington’s disease. Neurodegeneration 3:169–173Google Scholar
  70. Folstein SE (1989) Huntington’s disease: a disorder of families. Johns Hopkins University Press, BaltimoreGoogle Scholar
  71. Forno LS, Jose C (1973) Huntington’s chorea: A pathological study. In: Barbeau A, Chase TN, Paulson GW (eds) Adv Neurol, vol 1., vol 1Raven, New York, pp 453–470Google Scholar
  72. Friedman JH, Trieschmann ME, Myers RH, Fernandez HH (2005) Monozygotic twins discordant for Huntington disease after 7 years. Arch Neurol 62(6):995–997PubMedGoogle Scholar
  73. Fujiyama F, Sohn J, Nakano T, Furuta T, Nakamura KC, Matsuda W, Kaneko T (2011) Exclusive and common targets of neostriatofugal projections of rat striosome neurons: a single neuron-tracing study using a viral vector. Eur J Neurosci 33(4):668–677PubMedGoogle Scholar
  74. Fusco FR, Chen Q, Lamoreaux WJ, Figueredo-Cardenas G, Jiao Y, Coffman JA, Surmeier DJ, Honig MG, Carlock LR, Reiner A (1999) Cellular localization of huntingtin in striatal and cortical neurons in rats: lack of correlation with neuronal vulnerability in Huntington’s disease. J Neurosci 19(4):1189–1202PubMedGoogle Scholar
  75. Georgiou N, Bradshaw JL, Chiu E, Tudor A, O’Gorman L, Phillips JG (1999) Differential clinical and motor control function in a pair of monozygotic twins with Huntington’s disease. Mov Disord 14(2):320–325PubMedGoogle Scholar
  76. Gerfen CR (1984) The neostriatal mosaic: compartmentalization of corticostriatal input and striatonigral output systems. Nature 311(5985):461–464PubMedGoogle Scholar
  77. Gerfen CR, Engber TM, Mahan LC, Susel Z, Chase TN, Monsma FJ Jr, Sibley DR (1990) D1 and D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons. Science 250(4986):1429–1432PubMedGoogle Scholar
  78. Glass M, Dragunow M, Faull RLM (2000) The pattern of neurodegeneration in Huntington’s disease: a comparative study of cannabinoid, dopamine, adenosine and GABA(A) receptor alterations in the human basal ganglia in Huntington’s disease. Neuroscience 97(3):505–519PubMedGoogle Scholar
  79. Glass M, Faull RLM, Dragunow M (1993) Loss of cannabinoid receptors in the substantia nigra in Huntington’s disease. Neuroscience 56(3):523–527PubMedGoogle Scholar
  80. Goldberg YP, Nicholson DW, Rasper DM, Kalchman MA, Koide HB, Graham RK, Bromm M, Kazemi-Esfarjani P, Thornberry NA, Vaillancourt JP, Hayden MR (1996) Cleavage of huntingtin by apopain, a proapoptotic cysteine protease, is modulated by the polyglutamine tract. Nat Genet 13(4):442–449PubMedGoogle Scholar
  81. Gomez-Esteban JC, Lezcano E, Zarranz JJ, Velasco F, Garamendi I, Perez T, Tijero B (2007) Monozygotic twins suffering from Huntington’s disease show different cognitive and behavioural symptoms. Eur Neurol 57(1):26–30PubMedGoogle Scholar
  82. Gomez-Tortosa E, Irizarry MC, Gomez-Isla T, Hyman BT (2000) Clinical and neuropathological correlates of dementia with Lewy bodies. Ann N Y Acad Sci 920:9–15PubMedGoogle Scholar
  83. Gomez-Tortosa E, MacDonald ME, Friend JC, Taylor SA, Weiler LJ, Cupples LA, Srinidhi J, Gusella JF, Bird ED, Vonsattel JP, Myers RH (2001) Quantitative neuropathological changes in presymptomatic Huntington’s disease. Ann Neurol 49(1):29–34PubMedGoogle Scholar
  84. Gong B, Lim MC, Wanderer J, Wyttenbach A, Morton AJ (2008) Time-lapse analysis of aggregate formation in an inducible PC12 cell model of Huntington’s disease reveals time-dependent aggregate formation that transiently delays cell death. Brain Res Bull 75(1):146–157PubMedGoogle Scholar
  85. Goto S, Hirano A, Rojas-Corona RR (1989) An immunohistochemical investigation of the human neostriatum in Huntington’s disease. Ann Neurol 25(3):298–304PubMedGoogle Scholar
  86. Graybiel AM (1990) Neurotransmitters and neuromodulators in the basal ganglia. Trends Neurosci 13(7):244–254PubMedGoogle Scholar
  87. Graybiel AM (1995) The basal ganglia. Trends Neurosci 18(2):60–62PubMedGoogle Scholar
  88. Graybiel AM, Ragsdale CW Jr (1978) Histochemically distinct compartments in the striatum of human, monkeys, and cat demonstrated by acetylthiocholinesterase staining. Proc Natl Acad Sci U S A 75(11):5723–5726PubMedCentralPubMedGoogle Scholar
  89. Graybiel AM, Ragsdale CW Jr, Edley SM (1979) Compartments in the striatum of the cat observed by retrograde cell labeling. Exp Brain Res 34(1):189–195PubMedGoogle Scholar
  90. Greenamyre JT, Penney JB, Young AB, D’Amato CJ, Hicks SP, Shoulson I (1985) Alterations in L-glutamate binding in Alzheimer’s and Huntington’s diseases. Science 227(4693):1496–1499PubMedGoogle Scholar
  91. Gu X, Andre VM, Cepeda C, Li SH, Li XJ, Levine MS, Yang XW (2007) Pathological cell-cell interactions are necessary for striatal pathogenesis in a conditional mouse model of Huntington’s disease. Mol Neurodegener 2:8PubMedCentralPubMedGoogle Scholar
  92. Gu X, Li C, Wei W, Lo V, Gong S, Li SH, Iwasato T, Itohara S, Li XJ, Mody I, Heintz N, Yang XW (2005) Pathological cell-cell interactions elicited by a neuropathogenic form of mutant Huntingtin contribute to cortical pathogenesis in HD mice. Neuron 46(3):433–444PubMedGoogle Scholar
  93. Guo Z, Rudow G, Pletnikova O, Codispoti KE, Orr BA, Crain BJ, Duan W, Margolis RL, Rosenblatt A, Ross CA, Troncoso JC (2012) Striatal neuronal loss correlates with clinical motor impairment in Huntington’s disease. Mov Disord 27(11):1379–1386PubMedCentralPubMedGoogle Scholar
  94. Gutekunst CA, Li SH, Yi H, Mulroy JS, Kuemmerle S, Jones R, Rye D, Ferrante RJ, Hersch SM, Li XJ (1999) Nuclear and neuropil aggregates in Huntington’s disease: relationship to neuropathology. J Neurosci 19(7):2522–2534PubMedGoogle Scholar
  95. Hadzi TC, Hendricks AE, Latourelle JC, Lunetta KL, Cupples LA, Gillis T, Mysore JS, Gusella JF, Macdonald ME, Myers RH, Vonsattel JP (2012) Assessment of cortical and striatal involvement in 523 Huntington disease brains. NeurologyGoogle Scholar
  96. Hallervorden J (1957) Huntingtonsche Chorea (Chorea chronica progressiva hereditaria). Handbuch der speziellen pathologischen Anatomie und Histologie (XIII/1 Bandteil A). Springer Verlag, Berlin. Göttingen. Heidelberg, pp 793–822Google Scholar
  97. Halliday GM, McRitchie DA, Macdonald V, Double KL, Trent RJ, McCusker E (1998) Regional specificity of brain atrophy in Huntington’s disease. Experimental Neurology 154(2):663–672PubMedGoogle Scholar
  98. Harper PS, Morris MR, Quarrell OWJ, Shaw DJ, Tyler A, Youngman S (1991) The clinical neurology of Huntington’s disease. Huntington’s Disease Major Problems in Neurology, 22. W.B. Saunders Company LTD, London Philadelphia Toronto Sydney Tokyo, pp 37–80Google Scholar
  99. Harrington KM, Kowall NW (1991) Parvalbumin immunoreactive neurons resist degeneration in Huntington’s disease striatum. J Neuropath Exp Neurol 50:309Google Scholar
  100. Hedreen JC, Folstein SE (1995) Early loss of neostriatal striosome neurons in Huntington’s disease. J Neuropathol Exp Neurol 54(1):105–120PubMedGoogle Scholar
  101. Hedreen JC, Peyser CE, Folstein SE, Ross CA (1991) Neuronal loss in layers V and VI of cerebral cortex in Huntington’s disease. Neuroscience Letters 133(2):257–261PubMedGoogle Scholar
  102. Heinsen H, Rub U, Bauer M, Ulmar G, Bethke B, Schuler M, Bocker F, Eisenmenger W, Gotz M, Korr H, Schmitz C (1999) Nerve cell loss in the thalamic mediodorsal nucleus in Huntington’s disease. Acta Neuropathol 97(6):613–622PubMedGoogle Scholar
  103. Heinsen H, Rub U, Gangnus D, Jungkunz G, Bauer M, Ulmar G, Bethke B, Schuler M, Bocker F, Eisenmenger W, Gotz M, Strik M (1996) Nerve cell loss in the thalamic centromedian-parafascicular complex in patients with Huntington’s disease. Acta Neuropathol 91(2):161–168PubMedGoogle Scholar
  104. Heinsen H, Strik M, Bauer M, Luther K, Ulmar G, Gangnus D, Jungkunz G, Eisenmenger W, Gotz M (1994) Cortical and striatal neurone number in Huntington’s disease. Acta Neuropathol 88(4):320–333PubMedGoogle Scholar
  105. Herndon ES, Hladik CL, Shang P, Burns DK, Raisanen J, White CL 3rd (2009) Neuroanatomic profile of polyglutamine immunoreactivity in Huntington disease brains. J Neuropathol Exp Neurol 68(3):250–261PubMedCentralPubMedGoogle Scholar
  106. Hilditch-Maguire P, Trettel F, Passani LA, Auerbach A, Persichetti F, MacDonald ME (2000) Huntingtin: an iron-regulated protein essential for normal nuclear and perinuclear organelles. Hum Mol Genet 9(19):2789–2797PubMedGoogle Scholar
  107. Hobbs NZ, Pedrick AV, Say MJ, Frost C, Santos RD, Coleman A, Sturrock A, Craufurd D, Stout JC, Leavitt BR, Barnes J, Tabrizi SJ, Scahill RI (2011) The structural involvement of the cingulate cortex in premanifest and early Huntington’s disease. Mov Disord 26(9):1684–1690PubMedGoogle Scholar
  108. Hodges A, Strand AD, Aragaki AK, Kuhn A, Sengstag T, Hughes G, Elliston LA, Hartog C, Goldstein DR, Thu D, Hollingsworth ZR, Collin F, Synek B, Holmans PA, Young AB, Wexler NS, Delorenzi M, Kooperberg C, Augood SJ, Faull RLM, Olson JM, Jones L, Luthi-Carter R (2006) Regional and cellular gene expression changes in human Huntington’s disease brain. Hum Mol Genet 15(6):965–977PubMedGoogle Scholar
  109. Hodgson JG, Agopyan N, Gutekunst CA, Leavitt BR, LePiane F, Singaraja R, Smith DJ, Bissada N, McCutcheon K, Nasir J, Jamot L, Li XJ, Stevens ME, Rosemond E, Roder JC, Phillips AG, Rubin EM, Hersch SM, Hayden MR (1999) A YAC mouse model for Huntington’s disease with full-length mutant huntingtin, cytoplasmic toxicity, and selective striatal neurodegeneration. Neuron 23(1):181–192PubMedGoogle Scholar
  110. Holt DJ, Graybiel AM, Saper CB (1997) Neurochemical architecture of the human striatum. J Comp Neurol 384(1):1–25PubMedGoogle Scholar
  111. Holt DJ, Hersh LB, Saper CB (1996) Cholinergic innervation in the human striatum: a three-compartment model. Neuroscience 74(1):67–87PubMedGoogle Scholar
  112. Huang K, Yanai A, Kang R, Arstikaitis P, Singaraja RR, Metzler M, Mullard A, Haigh B, Gauthier-Campbell C, Gutekunst CA, Hayden MR, El-Husseini A (2004) Huntingtin-interacting protein HIP14 is a palmitoyl transferase involved in palmitoylation and trafficking of multiple neuronal proteins. Neuron 44(6):977–986PubMedGoogle Scholar
  113. Hult S, Schultz K, Soylu R, Petersen A (2010) Hypothalamic and neuroendocrine changes in Huntington’s disease. Curr Drug Targets 11(10):1237–1249PubMedGoogle Scholar
  114. Hunt MJ, Morton AJ (2005) Atypical diabetes associated with inclusion formation in the R6/2 mouse model of Huntington’s disease is not improved by treatment with hypoglycaemic agents. Exp Brain Res 166(2):220–229PubMedGoogle Scholar
  115. Huntington Study Group (1996) Unified Huntington’s Disease Rating Scale: reliability and consistency. Mov Disord 11(2):136–142Google Scholar
  116. Jernigan TL, Salmon DP, Butters N, Hesselink JR (1991) Cerebral structure on MRI, Part II: Specific changes in Alzheimer’s and Huntington’s diseases. Biol Psychiatry 29(1):68–81PubMedGoogle Scholar
  117. Jervis GA (1963) Huntington’s Chorea in childhood. Arch Neurol 9:244–257PubMedGoogle Scholar
  118. Jeste DV, Barban L, Parisi J (1984) Reduced Purkinje cell density in Huntington’s disease. Exp Neurol 85(1):78–86PubMedGoogle Scholar
  119. Joyce JN, Lexow N, Bird E, Winokur A (1988) Organization of dopamine D1 and D2 receptors in human striatum: receptor autoradiographic studies in Huntington’s disease and schizophrenia. Synapse 2(5):546–557PubMedGoogle Scholar
  120. Kaltenbach LS, Romero E, Becklin RR, Chettier R, Bell R, Phansalkar A, Strand A, Torcassi C, Savage J, Hurlburt A, Cha GH, Ukani L, Chepanoske CL, Zhen Y, Sahasrabudhe S, Olson J, Kurschner C, Ellerby LM, Peltier JM, Botas J, Hughes RE (2007) Huntingtin interacting proteins are genetic modifiers of neurodegeneration. PLoS Genet 3(5):e82PubMedCentralPubMedGoogle Scholar
  121. Kam M, Curtis MA, McGlashan SR, Connor B, Nannmark U, Faull RLM (2009) The cellular composition and morphological organization of the rostral migratory stream in the adult human brain. J Chem Neuroanat 37(3):196–205PubMedGoogle Scholar
  122. Kassubek J, Gaus W, Landwehrmeyer GB (2004) Evidence for more widespread cerebral pathology in early HD: an MRI-based morphometric analysis. Neurology 62(3):523–524PubMedGoogle Scholar
  123. Kassubek J, Juengling FD, Ecker D, Landwehrmeyer GB (2005) Thalamic atrophy in Huntington’s disease co-varies with cognitive performance: a morphometric MRI analysis. Cereb Cortex 15(6):846–853PubMedGoogle Scholar
  124. Kayahara T, Nakano K (1996) Pallido-thalamo-motor cortical connections: an electron microscopic study in the macaque monkey. Brain Res 706(2):337–342PubMedGoogle Scholar
  125. Kegel KB, Meloni AR, Yi Y, Kim YJ, Doyle E, Cuiffo BG, Sapp E, Wang Y, Qin ZH, Chen JD, Nevins JR, Aronin N, DiFiglia M (2002) Huntingtin is present in the nucleus, interacts with the transcriptional corepressor C-terminal binding protein, and represses transcription. J Biol Chem 277(9):7466–7476PubMedGoogle Scholar
  126. Khan ZU, Gutierrez A, Martin R, Penafiel A, Rivera A, De La Calle A (1998) Differential regional and cellular distribution of dopamine D2-like receptors: an immunocytochemical study of subtype-specific antibodies in rat and human brain. J Comp Neurol 402(3):353–371PubMedGoogle Scholar
  127. Kiesselbach G (1914) Anatomischer Befund eines Falles von Huntingtonscher Chorea. MonatsschrPsychiatNeurol 35:525–543Google Scholar
  128. Kitamura A, Kubota H, Pack CG, Matsumoto G, Hirayama S, Takahashi Y, Kimura H, Kinjo M, Morimoto RI, Nagata K (2006) Cytosolic chaperonin prevents polyglutamine toxicity with altering the aggregation state. Nat Cell Biol 8(10):1163–1170PubMedGoogle Scholar
  129. Kowall NW, Quigley BJ Jr, Krause JE, Lu F, Kosofsky BE, Ferrante RJ (1993) Substance P and substance P receptor histochemistry in human neurodegenerative diseases. Regul Pept 46(1–2):174–185PubMedGoogle Scholar
  130. Kremer HP (1992) The hypothalamic lateral tuberal nucleus: normal anatomy and changes in neurological diseases. Prog Brain Res 93:249–261PubMedGoogle Scholar
  131. Kremer HP, Roos RA, Dingjan G, Marani E, Bots GT (1990) Atrophy of the hypothalamic lateral tuberal nucleus in Huntington’s disease. J Neuropathol Exp Neurol 49(4):371–382PubMedGoogle Scholar
  132. Kremer HP, Roos RA, Dingjan GM, Bots GT, Bruyn GW, Hofman MA (1991) The hypothalamic lateral tuberal nucleus and the characteristics of neuronal loss in Huntington’s disease. Neurosci Lett 132(1):101–104PubMedGoogle Scholar
  133. Kuemmerle S, Gutekunst CA, Klein AM, Li XJ, Li SH, Beal MF, Hersch SM, Ferrante RJ (1999) Huntington aggregates may not predict neuronal death in Huntington’s disease. Ann Neurol 46(6):842–849PubMedGoogle Scholar
  134. Kuppenbender KD, Standaert DG, Feuerstein TJ, Penney JB Jr, Young AB, Landwehrmeyer GB (2000) Expression of NMDA receptor subunit mRNAs in neurochemically identified projection and interneurons in the human striatum. J Comp Neurol 419(4):407–421PubMedGoogle Scholar
  135. Laforet GA, Sapp E, Chase K, McIntyre C, Boyce FM, Campbell M, Cadigan BA, Warzecki L, Tagle DA, Reddy PH, Cepeda C, Calvert CR, Jokel ES, Klapstein GJ, Ariano MA, Levine MS, DiFiglia M, Aronin N (2001) Changes in cortical and striatal neurons predict behavioral and electrophysiological abnormalities in a transgenic murine model of Huntington’s disease. J Neurosci 21(23):9112–9123PubMedGoogle Scholar
  136. Lalic NM, Maric J, Svetel M, Jotic A, Stefanova E, Lalic K, Dragasevic N, Milicic T, Lukic L, Kostic VS (2008) Glucose homeostasis in Huntington disease: abnormalities in insulin sensitivity and early-phase insulin secretion. Arch Neurol 65(4):476–480PubMedGoogle Scholar
  137. Landles C, Bates GP (2004) Huntingtin and the molecular pathogenesis of Huntington’s disease. Fourth in molecular medicine review series. EMBO Rep 5(10):958–963PubMedCentralPubMedGoogle Scholar
  138. Landles C, Sathasivam K, Weiss A, Woodman B, Moffitt H, Finkbeiner S, Sun B, Gafni J, Ellerby LM, Trottier Y, Richards WG, Osmand A, Paganetti P, Bates GP (2010) Proteolysis of mutant huntingtin produces an exon 1 fragment that accumulates as an aggregated protein in neuronal nuclei in Huntington disease. J Biol Chem 285(12):8808–8823PubMedCentralPubMedGoogle Scholar
  139. Lange H, Thorner G, Hopf A, Schroder KF (1976) Morphometric studies of the neuropathological changes in choreatic diseases. J Neurol Sci 28(4):401–425PubMedGoogle Scholar
  140. Lanska DJ, Lanska MJ, Lavine L, Schoenberg BS (1988) Conditions associated with Huntington’s disease at death. A case-control study. Arch Neurol 45(8):878–880Google Scholar
  141. Lewy FH (1923) Die Histopathologie der choreatischen Erkrankungen. Zeitschrift für die gesamte Neurologie und Psychiatrie (Berlin) 85:622–658Google Scholar
  142. Li JY, Plomann M, Brundin P (2003) Huntington’s disease: a synaptopathy? Trends Mol Med 9(10):414–420PubMedGoogle Scholar
  143. Li SH, Li XJ (2004) Huntingtin-protein interactions and the pathogenesis of Huntington’s disease. Trends Genet 20(3):146–154PubMedGoogle Scholar
  144. Lievens JC, Iche M, Laval M, Faivre-Sarrailh C, Birman S (2008) AKT-sensitive or insensitive pathways of toxicity in glial cells and neurons in Drosophila models of Huntington’s disease. Hum Mol Genet 17(6):882–894PubMedGoogle Scholar
  145. Low VF, Dragunow M, Tippett LJ, Faull RLM, Curtis MA (2011) No change in progenitor cell proliferation in the hippocampus in Huntington’s disease. Neuroscience 199:577–588PubMedGoogle Scholar
  146. Lunkes A, Lindenberg KS, Ben-Haiem L, Weber C, Devys D, Landwehrmeyer GB, Mandel JL, Trottier Y (2002) Proteases acting on mutant huntingtin generate cleaved products that differentially build up cytoplasmic and nuclear inclusions. Mol Cell 10(2):259–269PubMedGoogle Scholar
  147. Luthi-Carter R, Strand A, Peters NL, Solano SM, Hollingsworth ZR, Menon AS, Frey AS, Spektor BS, Penney EB, Schilling G, Ross CA, Borchelt DR, Tapscott SJ, Young AB, Cha JH, Olson JM (2000) Decreased expression of striatal signaling genes in a mouse model of Huntington’s disease. Hum Mol Genet 9(9):1259–1271PubMedGoogle Scholar
  148. Maat-Schieman ML, Dorsman JC, Smoor MA, Siesling S, Van Duinen SG, Verschuuren JJ, den Dunnen JT, Van Ommen GJ, Roos RA (1999) Distribution of inclusions in neuronal nuclei and dystrophic neurites in Huntington disease brain. J Neuropathol Exp Neurol 58(2):129–137PubMedGoogle Scholar
  149. Macdonald V, Halliday GM (2002) Pyramidal cell loss in motor cortices in Huntington’s disease. Neurobiology of Disease 10(3):378–386PubMedGoogle Scholar
  150. Macdonald V, Halliday GM, Trent RJ, McCusker EA (1997) Significant loss of pyramidal neurons in the angular gyrus of patients with Huntington’s disease. Neuropathol Appl Neurobiol 23(6):492–495PubMedGoogle Scholar
  151. Machida Y, Okada T, Kurosawa M, Oyama F, Ozawa K, Nukina N (2006) rAAV-mediated shRNA ameliorated neuropathology in Huntington disease model mouse. Biochem Biophys Res Commun 343(1):190–197PubMedGoogle Scholar
  152. MacMillan JC, Snell RG, Tyler A, Houlihan GD, Fenton I, Cheadle JP, Lazarou LP, Shaw DJ, Harper PS (1993) Molecular analysis and clinical correlations of the Huntington’s disease mutation. Lancet 342(8877):954–958PubMedGoogle Scholar
  153. Manley MS, Young SJ, Groves PM (1994) Compartmental organization of the peptide network in the human caudate nucleus. J Chem Neuroanat 7(3):191–201PubMedGoogle Scholar
  154. Markham CH, Knox JW (1965) Observations on Huntington’s Chorea in Childhood. J Pediatr 67:46–57PubMedGoogle Scholar
  155. Marshall PE, Landis DM, Zalneraitis EL (1983) Immunocytochemical studies of substance P and leucine-enkephalin in Huntington’s disease. Brain Res 289(1–2):11–26PubMedGoogle Scholar
  156. Martindale D, Hackam A, Wieczorek A, Ellerby L, Wellington C, McCutcheon K, Singaraja R, Kazemi-Esfarjani P, Devon R, Kim SU, Bredesen DE, Tufaro F, Hayden MR (1998) Length of huntingtin and its polyglutamine tract influences localization and frequency of intracellular aggregates. Nat Genet 18(2):150–154PubMedGoogle Scholar
  157. McCaughey WTE (1961) The pathologic spectrum of Huntington’s chorea. J Nerv Ment Dis 133:91–103Google Scholar
  158. McGeorge AJ, Faull RLM (1989) The organization of the projection from the cerebral cortex to the striatum in the rat. Neuroscience 29(3):503–537PubMedGoogle Scholar
  159. Mehler WR (1971) Idea of a new anatomy of the thalamus. J Psychiatr Res 8(3):203–217PubMedGoogle Scholar
  160. Mena-Segovia J, Bolam JP, Magill PJ (2004) Pedunculopontine nucleus and basal ganglia: distant relatives or part of the same family? Trends Neurosci 27(10):585–588PubMedGoogle Scholar
  161. Molyneaux BJ, Arlotta P, Menezes JR, Macklis JD (2007) Neuronal subtype specification in the cerebral cortex. Nat Rev Neurosci 8(6):427–437PubMedGoogle Scholar
  162. Montoya A, Price BH, Menear M, Lepage M (2006) Brain imaging and cognitive dysfunctions in Huntington’s disease. J Psychiatry Neurosci 31(1):21–29PubMedCentralPubMedGoogle Scholar
  163. Morton AJ, Faull RLM, Edwardson JM (2001) Abnormalities in the synaptic vesicle fusion machinery in Huntington’s disease. Brain Res Bull 56(2):111–117PubMedGoogle Scholar
  164. Morton AJ, Nicholson LF, Faull RLM (1993) Compartmental loss of NADPH diaphorase in the neuropil of the human striatum in Huntington’s disease. Neuroscience 53(1):159–168PubMedGoogle Scholar
  165. Morton AJ, Wood NI, Hastings MH, Hurelbrink C, Barker RA, Maywood ES (2005) Disintegration of the sleep-wake cycle and circadian timing in Huntington’s disease. J Neurosci 25(1):157–163PubMedGoogle Scholar
  166. Myers RH, Sax DS, Koroshetz WJ, Mastromauro C, Cupples LA, Kiely DK, Pettengill FK, Bird ED (1991a) Factors associated with slow progression in Huntington’s disease. Arch Neurol 48(8):800–804PubMedGoogle Scholar
  167. Myers RH, Vonsattel JP, Paskevich PA, Kiely DK, Stevens TJ, Cupples LA, Richardson EP Jr, Bird ED (1991b) Decreased neuronal and increased oligodendroglial densities in Huntington’s disease caudate nucleus. J Neuropathol Exp Neurol 50(6):729–742PubMedGoogle Scholar
  168. Nambu A, Tokuno H, Takada M (2002) Functional significance of the cortico-subthalamo-pallidal ‘hyperdirect’ pathway. Neurosci Res 43(2):111–117PubMedGoogle Scholar
  169. Nauta WJ, Domesick VB (1984) Afferent and efferent relationships of the basal ganglia. Ciba Found Symp 107:3–29PubMedGoogle Scholar
  170. Neustaedter M (1933) Concerning the striatal localization in chronic progressive chorea. With a report of three cases, two of the Huntington type in siblings and one senile arteriosclerotic, with necropsies. Journal of Nervous and Mental Disease 78:470–491Google Scholar
  171. Nopoulos P, Aylward EH, Ross CA, Johnson HJ, Magnotta VA, Juhl AR, Pierson RK, Mills J, Langbehn DR, Paulsen JS (2010) Cerebral cortex structure in prodromal Huntington disease. Neurobiol Dis 40(3):544–554PubMedCentralPubMedGoogle Scholar
  172. Nopoulos P, Magnotta VA, Mikos A, Paulson H, Andreasen NC, Paulsen JS (2007) Morphology of the cerebral cortex in preclinical Huntington’s disease. Am J Psychiatry 164(9):1428–1434PubMedGoogle Scholar
  173. Ouimet CC, Langley-Gullion KC, Greengard P (1998) Quantitative immunocytochemistry of DARPP-32-expressing neurons in the rat caudatoputamen. Brain Res 808(1):8–12PubMedGoogle Scholar
  174. Oyanagi K, Ikuta F (1987) A morphometric reevaluation of Huntington’s chorea with special reference to the large neurons in the neostriatum. Clin Neuropathol 6(2):71–79PubMedGoogle Scholar
  175. Oyanagi K, Takeda S, Takahashi H, Ohama E, Ikuta F (1989) A quantitative investigation of the substantia nigra in Huntington’s disease. Ann Neurol 26(1):13–19PubMedGoogle Scholar
  176. Parent A, Cote PY, Lavoie B (1995) Chemical anatomy of primate basal ganglia. Prog Neurobiol 46(2–3):131–197PubMedGoogle Scholar
  177. Parent A, Fortin M, Cote PY, Cicchetti F (1996) Calcium-binding proteins in primate basal ganglia. Neurosci Res 25(4):309–334PubMedGoogle Scholar
  178. Parent A, Hazrati LN (1993) Anatomical aspects of information processing in primate basal ganglia. Trends Neurosci 16(3):111–116PubMedGoogle Scholar
  179. Parent A, Hazrati LN (1995) Functional anatomy of the basal ganglia. I. The cortico-basal ganglia-thalamo-cortical loop. Brain Res Brain Res Rev 20(1):91–127PubMedGoogle Scholar
  180. Paulsen JS (2009) Functional imaging in Huntington’s disease. Exp Neurol 216(2):272–277PubMedGoogle Scholar
  181. Pavese N, Gerhard A, Tai YF, Ho AK, Turkheimer F, Barker RA, Brooks DJ, Piccini P (2006) Microglial activation correlates with severity in Huntington disease: a clinical and PET study. Neurology 66(11):1638–1643PubMedGoogle Scholar
  182. Penney JB Jr, Young AB (1982) Quantitative autoradiography of neurotransmitter receptors in Huntington disease. Neurology 32(12):1391–1395PubMedGoogle Scholar
  183. Perutz MF (1996) Glutamine repeats and inherited neurodegenerative diseases: molecular aspects. Curr Opin Struct Biol 6(6):848–858PubMedGoogle Scholar
  184. Perutz MF, Johnson T, Suzuki M, Finch JT (1994) Glutamine repeats as polar zippers: their possible role in inherited neurodegenerative diseases. Proc Natl Acad Sci USA 91(12):5355–5358PubMedCentralPubMedGoogle Scholar
  185. Petersen A, Bjorkqvist M (2006) Hypothalamic-endocrine aspects in Huntington’s disease. Eur J Neurosci 24(4):961–967PubMedGoogle Scholar
  186. Petersen A, Gil J, Maat-Schieman ML, Bjorkqvist M, Tanila H, Araujo IM, Smith R, Popovic N, Wierup N, Norlen P, Li JY, Roos RA, Sundler F, Mulder H, Brundin P (2005) Orexin loss in Huntington’s disease. Hum Mol Genet 14(1):39–47PubMedGoogle Scholar
  187. Pillai JA, Hansen LA, Masliah E, Goldstein JL, Edland SD, Corey-Bloom J (2012) Clinical severity of Huntington’s disease does not always correlate with neuropathologic stage. Mov Disord 27(9):1099–1103PubMedCentralPubMedGoogle Scholar
  188. Podolsky S, Leopold NA, Sax DS (1972) Increased frequency of diabetes mellitus in patients with Huntington’s chorea. Lancet 1(7765):1356–1358PubMedGoogle Scholar
  189. Politis M, Pavese N, Tai YF, Tabrizi SJ, Barker RA, Piccini P (2008) Hypothalamic involvement in Huntington’s disease: an in vivo PET study. Brain 131(Pt 11):2860–2869PubMedGoogle Scholar
  190. Prensa L, Gimenez-Amaya JM, Parent A (1999) Chemical heterogeneity of the striosomal compartment in the human striatum. J Comp Neurol 413(4):603–618PubMedGoogle Scholar
  191. Rajkowska G, Selemon LD, Goldman-Rakic PS (1998) Neuronal and glial somal size in the prefrontal cortex: a postmortem morphometric study of schizophrenia and Huntington disease. Arch Gen Psychiatry 55(3):215–224PubMedGoogle Scholar
  192. Ratovitski T, Gucek M, Jiang H, Chighladze E, Waldron E, D’Ambola J, Hou Z, Liang Y, Poirier MA, Hirschhorn RR, Graham R, Hayden MR, Cole RN, Ross CA (2009) Mutant huntingtin N-terminal fragments of specific size mediate aggregation and toxicity in neuronal cells. J Biol Chem 284(16):10855–10867PubMedCentralPubMedGoogle Scholar
  193. Reading SA, Yassa MA, Bakker A, Dziorny AC, Gourley LM, Yallapragada V, Rosenblatt A, Margolis RL, Aylward EH, Brandt J, Mori S, van Zijl P, Bassett SS, Ross CA (2005) Regional white matter change in pre-symptomatic Huntington’s disease: a diffusion tensor imaging study. Psychiatry Res 140(1):55–62PubMedGoogle Scholar
  194. Reiner A, Albin RL, Anderson KD, D’Amato CJ, Penney JB, Young AB (1988) Differential loss of striatal projection neurons in Huntington disease. Proc Natl Acad Sci USA 85(15):5733–5737PubMedCentralPubMedGoogle Scholar
  195. Reiner A, Del Mar N, Deng YP, Meade CA, Sun Z, Goldowitz D (2007) R6/2 neurons with intranuclear inclusions survive for prolonged periods in the brains of chimeric mice. J Comp Neurol 505(6):603–629PubMedGoogle Scholar
  196. Reiner A, Shelby E, Wang H, Demarch Z, Deng Y, Guley NH, Hogg V, Roxburgh R, Tippett LJ, Waldvogel HJ, Faull RL (2013) Striatal parvalbuminergic neurons are lost in Huntington’s disease: implications for dystonia. Mov Disord 28(12):1691–1699PubMedCentralPubMedGoogle Scholar
  197. Reisine TD, Fields JZ, Bird ED, Spokes E, Yamamura HI (1978) Characterization of brain dopaminergic receptors in Huntington’s disease. Commun Psychopharmacol 2(2):79–84PubMedGoogle Scholar
  198. Ribchester RR, Thomson D, Wood NI, Hinks T, Gillingwater TH, Wishart TM, Court FA, Morton AJ (2004) Progressive abnormalities in skeletal muscle and neuromuscular junctions of transgenic mice expressing the Huntington’s disease mutation. Eur J Neurosci 20(11):3092–3114PubMedGoogle Scholar
  199. Richardson EP Jr (1990) Huntington’s disease: some recent neuropathological studies. Neuropathol Appl Neurobiol 16(6):451–460PubMedGoogle Scholar
  200. Richfield EK, Herkenham M (1994) Selective vulnerability in Huntington’s disease: preferential loss of cannabinoid receptors in lateral globus pallidus. Ann Neurol 36(4):577–584PubMedGoogle Scholar
  201. Richfield EK, O’Brien CF, Eskin T, Shoulson I (1991) Heterogeneous dopamine receptor changes in early and late Huntington’s disease. Neurosci Lett 132(1):121–126PubMedGoogle Scholar
  202. Rodda RA (1981) Cerebellar atrophy in Huntington’s disease. J Neurol Sci 50(1):147–157PubMedGoogle Scholar
  203. Rodriguez-Lebron E, Denovan-Wright EM, Nash K, Lewin AS, Mandel RJ (2005) Intrastriatal rAAV-mediated delivery of anti-huntingtin shRNAs induces partial reversal of disease progression in R6/1 Huntington’s disease transgenic mice. Mol Ther 12(4):618–633PubMedCentralPubMedGoogle Scholar
  204. Roizin L, Kaufman MA, Willson N, Stellar S, Liu JC (1976) Neuropathologic observations in Huntington’s chorea. In: Zimmerman HM (ed) Progress in neuropathology, vol 3. Grune and Stratton, New York, pp 447–488Google Scholar
  205. Roizin L, Stellar S, Liu JC (1979) Neuronal nuclear and cytoplasmic changes in Huntington’s chorea: Electron microscope investigations. In: Chase TN, Wexler NS, Barbeau A (eds) Huntington’s disease. Advances in neurology, vol 23. Raven Press, New York, pp 95–122Google Scholar
  206. Roos RA, Pruyt JF, de Vries J, Bots GT (1985) Neuronal distribution in the putamen in Huntington’s disease. J Neurol Neurosurg Psychiatry 48(5):422–425PubMedCentralPubMedGoogle Scholar
  207. Rosas HD, Hevelone ND, Zaleta AK, Greve DN, Salat DH, Fischl B (2005) Regional cortical thinning in preclinical Huntington disease and its relationship to cognition. Neurology 65(5):745–747PubMedGoogle Scholar
  208. Rosas HD, Koroshetz WJ, Chen YI, Skeuse C, Vangel M, Cudkowicz ME, Caplan K, Marek K, Seidman LJ, Makris N, Jenkins BG, Goldstein JM (2003) Evidence for more widespread cerebral pathology in early HD: an MRI-based morphometric analysis. Neurology 60(10):1615–1620PubMedGoogle Scholar
  209. Rosas HD, Lee SY, Bender AC, Zaleta AK, Vangel M, Yu P, Fischl B, Pappu V, Onorato C, Cha JH, Salat DH, Hersch SM (2010) Altered white matter microstructure in the corpus callosum in Huntington’s disease: implications for cortical “disconnection”. Neuroimage 49(4):2995–3004PubMedGoogle Scholar
  210. Rosas HD, Liu AK, Hersch S, Glessner M, Ferrante RJ, Salat DH, van der Kouwe A, Jenkins BG, Dale AM, Fischl B (2002) Regional and progressive thinning of the cortical ribbon in Huntington’s disease. Neurology 58(5):695–701PubMedGoogle Scholar
  211. Rosas HD, Salat DH, Lee SY, Zaleta AK, Pappu V, Fischl B, Greve D, Hevelone ND, Hersch SM (2008) Cerebral cortex and the clinical expression of Huntington’s disease: complexity and heterogeneity. Brain 131(Pt 4):1057–1068PubMedCentralPubMedGoogle Scholar
  212. Rosas HD, Tuch DS, Hevelone ND, Zaleta AK, Vangel M, Hersch SM, Salat DH (2006) Diffusion tensor imaging in presymptomatic and early Huntington’s disease: Selective white matter pathology and its relationship to clinical measures. Mov Disord 21(9):1317–1325PubMedGoogle Scholar
  213. Ross CA, Poirier MA (2004) Protein aggregation and neurodegenerative disease. Nat Med 10(Suppl):S10–17PubMedGoogle Scholar
  214. Rüb U, Hoche F, Brunt ER, Heinsen H, Seidel K, Del Turco D, Paulson HL, Bohl J, von Gall C, Vonsattel JP, Korf HW, den Dunnen WF (2013) Degeneration of the cerebellum in Huntington’s disease (HD): possible relevance for the clinical picture and potential gateway to pathological mechanisms of the disease process. Brain Pathol 23(2):165–177PubMedGoogle Scholar
  215. Ruocco HH, Bonilha L, Li LM, Lopes-Cendes I, Cendes F (2008) Longitudinal analysis of regional grey matter loss in Huntington disease: effects of the length of the expanded CAG repeat. J Neurol Neurosurg Psychiatry 79(2):130–135PubMedGoogle Scholar
  216. Sadikot AF, Parent A, Smith Y, Bolam JP (1992) Efferent connections of the centromedian and parafascicular thalamic nuclei in the squirrel monkey: a light and electron microscopic study of the thalamostriatal projection in relation to striatal heterogeneity. J Comp Neurol 320(2):228–242PubMedGoogle Scholar
  217. Sapp E, Kegel KB, Aronin N, Hashikawa T, Uchiyama Y, Tohyama K, Bhide PG, Vonsattel JP, DiFiglia M (2001) Early and progressive accumulation of reactive microglia in the Huntington disease brain. J Neuropathol Exp Neurol 60(2):161–172PubMedGoogle Scholar
  218. Sapp E, Penney J, Young A, Aronin N, Vonsattel JP, DiFiglia M (1999) Axonal transport of N-terminal huntingtin suggests early pathology of corticostriatal projections in Huntington disease. J Neuropathol Exp Neurol 58(2):165–173PubMedGoogle Scholar
  219. Sapp E, Schwarz C, Chase K, Bhide PG, Young AB, Penney J, Vonsattel JP, Aronin N, DiFiglia M (1997) Huntingtin localization in brains of normal and Huntington’s disease patients. Ann Neurol 42(4):604–612PubMedGoogle Scholar
  220. Saudou F, Finkbeiner S, Devys D, Greenberg ME (1998) Huntingtin acts in the nucleus to induce apoptosis but death does not correlate with the formation of intranuclear inclusions. Cell 95(1):55–66PubMedGoogle Scholar
  221. Schiefer J, Landwehrmeyer GB, Luesse HG, Sprunken A, Puls C, Milkereit A, Milkereit E, Kosinski CM (2002) Riluzole prolongs survival time and alters nuclear inclusion formation in a transgenic mouse model of Huntington’s disease. Mov Disord 17(4):748–757PubMedGoogle Scholar
  222. Schroeder K (1931) Zur Klinik und Pathologie der Huntingtonschen Krankheit. J Psychol Neurol 43:183–201Google Scholar
  223. Selemon LD, Rajkowska G, Goldman-Rakic PS (2004) Evidence for progression in frontal cortical pathology in late-stage Huntington’s disease. J Comp Neurol 468(2):190–204PubMedGoogle Scholar
  224. Seto-Ohshima A, Emson PC, Lawson E, Mountjoy CQ, Carrasco LH (1988) Loss of matrix calcium-binding protein-containing neurons in Huntington’s disease. Lancet 1(8597):1252–1255PubMedGoogle Scholar
  225. Shin JY, Fang ZH, Yu ZX, Wang CE, Li SH, Li XJ (2005) Expression of mutant huntingtin in glial cells contributes to neuronal excitotoxicity. J Cell Biol 171(6):1001–1012PubMedCentralPubMedGoogle Scholar
  226. Sieradzan KA, Mann DM (2001) The selective vulnerability of nerve cells in Huntington’s disease. Neuropathol Appl Neurobiol 27(1):1–21PubMedGoogle Scholar
  227. Simmons DA, Casale M, Alcon B, Pham N, Narayan N, Lynch G (2007) Ferritin accumulation in dystrophic microglia is an early event in the development of Huntington’s disease. Glia 55(10):1074–1084PubMedGoogle Scholar
  228. Smith Y, Bevan MD, Shink E, Bolam JP (1998) Microcircuitry of the direct and indirect pathways of the basal ganglia. Neuroscience 86(2):353–387PubMedGoogle Scholar
  229. Smith Y, Raju DV, Pare JF, Sidibe M (2004) The thalamostriatal system: a highly specific network of the basal ganglia circuitry. Trends Neurosci 27(9):520–527PubMedGoogle Scholar
  230. Sotrel A, Paskevich PA, Kiely DK, Bird ED, Williams RS, Myers RH (1991) Morphometric analysis of the prefrontal cortex in Huntington’s disease. Neurology 41(7):1117–1123PubMedGoogle Scholar
  231. Sotrel A, Williams RS, Kaufmann WE, Myers RH (1993) Evidence for neuronal degeneration and dendritic plasticity in cortical pyramidal neurons of Huntington’s disease: a quantitative Golgi study. Neurology 43(10):2088–2096PubMedGoogle Scholar
  232. Spampanato J, Gu X, Yang XW, Mody I (2008) Progressive synaptic pathology of motor cortical neurons in a BAC transgenic mouse model of Huntington’s disease. Neuroscience 157(3):606–620PubMedCentralPubMedGoogle Scholar
  233. Spargo E, Everall IP, Lantos PL (1993) Neuronal loss in the hippocampus in Huntington’s disease: a comparison with HIV infection. J Neurol Neurosurg Psychiatry 56(5):487–491PubMedCentralPubMedGoogle Scholar
  234. Spielmeyer W (1926) Die anatomische Krankheitsforschung am Beispiel einer Huntingtonschen Chorea mit Wilsonschem Symptomenbild. Zeitschrift für die gesamte Neurologie und Psychiatrie (Berlin) 101:701–728Google Scholar
  235. Spokes EG (1980) Neurochemical alterations in Huntington’s chorea: a study of post-mortem brain tissue. Brain 103(1):179–210PubMedGoogle Scholar
  236. Strand AD, Baquet ZC, Aragaki AK, Holmans PA, Yang L, Cleren C, Beal MF, Jones L, Kooperberg C, Olson JM, Jones KR (2007) Expression profiling of Huntington’s disease models suggests that brain-derived neurotrophic factor depletion plays a major role in striatal degeneration. J Neurosci 27(43):11758–11768PubMedGoogle Scholar
  237. Tabrizi SJ, Scahill RI, Durr A, Roos RA, Leavitt BR, Jones R, Landwehrmeyer GB, Fox NC, Johnson H, Hicks SL, Kennard C, Craufurd D, Frost C, Langbehn DR, Reilmann R, Stout JC (2011) Biological and clinical changes in premanifest and early stage Huntington’s disease in the TRACK-HD study: the 12-month longitudinal analysis. Lancet Neurol 10(1):31–42PubMedGoogle Scholar
  238. Tai YF, Pavese N, Gerhard A, Tabrizi SJ, Barker RA, Brooks DJ, Piccini P (2007) Microglial activation in presymptomatic Huntington’s disease gene carriers. Brain 130(Pt 7):1759–1766PubMedGoogle Scholar
  239. Tattersfield AS, Croon RJ, Liu YW, Kells AP, Faull RLM, Connor B (2004) Neurogenesis in the striatum of the quinolinic acid lesion model of Huntington’s disease. Neuroscience 127(2):319–332PubMedGoogle Scholar
  240. Telenius H, Kremer B, Goldberg YP, Theilmann J, Andrew SE, Zeisler J, Adam S, Greenberg C, Ives EJ, Clarke LA et al (1994) Somatic and gonadal mosaicism of the Huntington disease gene CAG repeat in brain and sperm. Nat Genet 6(4):409–414PubMedGoogle Scholar
  241. Tellez-Nagel I, Johnson AB, Terry RD (1974) Studies on brain biopsies of patients with Huntington’s chorea. J Neuropathol Exp Neurol 33(2):308–332PubMedGoogle Scholar
  242. Terplan K (1924) Zur pathologischen Anatomie der chronischen progressiven Chorea. Virchow’s Arch f Pathol Anat (Berl) 252:146–176Google Scholar
  243. Thompson-Vest NM, Waldvogel HJ, Rees MI, Faull RL (2003) GABA(A) receptor subunit and gephyrin protein changes differ in the globus pallidus in Huntington’s diseased brain. Brain Res 994(2):265–270PubMedGoogle Scholar
  244. Thompson JC, Snowden JS, Craufurd D, Neary D (2002) Behavior in Huntington’s disease: dissociating cognition-based and mood-based changes. J Neuropsychiatry Clin Neurosci 14(1):37–43PubMedGoogle Scholar
  245. Thu DCV, Oorschot DE, Tippett LJ, Nana AL, Hogg VM, Synek BJ, Luthi-Carter R, Waldvogel HJ, Faull RLM (2010) Cell loss in the motor and cingulate cortex correlates with symptomatology in Huntington’s disease. Brain 133(Pt 4):1094–1110PubMedGoogle Scholar
  246. Timmers HJ, Swaab DF, van de Nes JA, Kremer HP (1996) Somatostatin 1-12 immunoreactivity is decreased in the hypothalamic lateral tuberal nucleus of Huntington’s disease patients. Brain Res 728(2):141–148PubMedGoogle Scholar
  247. Tippett LJ, Waldvogel HJ, Thomas SJ, Hogg VM, van Roon-Mom W, Synek BJ, Graybiel AM, Faull RLM (2007) Striosomes and mood dysfunction in Huntington’s disease. Brain 130(Pt 1):206–221PubMedGoogle Scholar
  248. Tokuno H, Chiken S, Kametani K, Moriizumi T (2002) Efferent projections from the striatal patch compartment: anterograde degeneration after selective ablation of neurons expressing mu-opioid receptor in rats. Neurosci Lett 332(1):5–8PubMedGoogle Scholar
  249. Trifiletti RR, Snowman AM, Whitehouse PJ, Marcus KA, Snyder SH (1987) Huntington’s disease: increased number and altered regulation of benzodiazepine receptor complexes in frontal cerebral cortex. Neurology 37(6):916–922PubMedGoogle Scholar
  250. Trottier Y, Lutz Y, Stevanin G, Imbert G, Devys D, Cancel G, Saudou F, Weber C, David G, Tora L et al (1995) Polyglutamine expansion as a pathological epitope in Huntington’s disease and four dominant cerebellar ataxias. Nature 378(6555):403–406PubMedGoogle Scholar
  251. Van der Burg JM, Bjorkqvist M, Brundin P (2009) Beyond the brain: widespread pathology in Huntington’s disease. Lancet Neurol 8(8):765–774PubMedGoogle Scholar
  252. Van Raamsdonk JM, Murphy Z, Selva DM, Hamidizadeh R, Pearson J, Petersen A, Bjorkqvist M, Muir C, Mackenzie IR, Hammond GL, Vogl AW, Hayden MR, Leavitt BR (2007) Testicular degeneration in Huntington disease. Neurobiol Dis 26(3):512–520PubMedGoogle Scholar
  253. Van Roon-Mom WM, Hogg VM, Tippett LJ, Faull RLM (2006) Aggregate distribution in frontal and motor cortex in Huntington’s disease brain. Neuroreport 17(6):667–670PubMedGoogle Scholar
  254. Vierbuchen T, Ostermeier A, Pang ZP, Kokubu Y, Sudhof TC, Wernig M (2010) Direct conversion of fibroblasts to functional neurons by defined factors. Nature 463(7284):1035–1041PubMedCentralPubMedGoogle Scholar
  255. Vogt C, Vogt O (1951) Precipitating and modifying agents in chorea. J Nerv Ment Dis 116:601–607Google Scholar
  256. Vonsattel JP, DiFiglia M (1998) Huntington disease. J Neuropathol Exp Neurol 57(5):369–384PubMedGoogle Scholar
  257. Vonsattel JP, Keller C, Cortes Ramirez EP (2011) Huntington’s disease—neuropathology. Handb Clin Neurol 100:83–100PubMedGoogle Scholar
  258. Vonsattel JP, Keller C, Del Pilar AM (2008) Neuropathology of Huntington’s disease. Handb Clin Neurol 89:599–618PubMedGoogle Scholar
  259. Vonsattel JP, Myers RH, Bird ED, Ge P, Richardson EP Jr (1992) Huntington disease: 7 cases with relatively preserved neostriatal islets. Rev Neurol (Paris) 148(2):107–116Google Scholar
  260. Vonsattel JP, Myers RH, Stevens TJ, Ferrante RJ, Bird ED, Richardson EP Jr (1985) Neuropathological classification of Huntington’s disease. J Neuropathol Exp Neurol 44(6):559–577PubMedGoogle Scholar
  261. Voorn P, Gerfen CR, Groenewegen HJ (1989) Compartmental organization of the ventral striatum of the rat: immunohistochemical distribution of enkephalin, substance P, dopamine, and calcium-binding protein. J Comp Neurol 289(2):189–201PubMedGoogle Scholar
  262. Waldvogel HJ, Faull RLM (1993) Compartmentalization of parvalbumin immunoreactivity in the human striatum. Brain Res 610(2):311–316PubMedGoogle Scholar
  263. Waldvogel HJ, Kubota Y, Fritschy J, Mohler H, Faull RLM (1999) Regional and cellular localisation of GABA(A) receptor subunits in the human basal ganglia: An autoradiographic and immunohistochemical study. J Comp Neurol 415(3):313–340PubMedGoogle Scholar
  264. Waters CM, Peck R, Rossor M, Reynolds GP, Hunt SP (1988) Immunocytochemical studies on the basal ganglia and substantia nigra in Parkinson’s disease and Huntington’s chorea. Neuroscience 25(2):419–438PubMedGoogle Scholar
  265. Watkins LH, Rogers RD, Lawrence AD, Sahakian BJ, Rosser AE, Robbins TW (2000) Impaired planning but intact decision making in early Huntington’s disease: implications for specific fronto-striatal pathology. Neuropsychologia 38(8):1112–1125PubMedGoogle Scholar
  266. Weeks RA, Piccini P, Harding AE, Brooks DJ (1996) Striatal D1 and D2 dopamine receptor loss in asymptomatic mutation carriers of Huntington’s disease. Ann Neurol 40(1):49–54PubMedGoogle Scholar
  267. Weiss A, Roscic A, Paganetti P (2009) Inducible mutant huntingtin expression in HN10 cells reproduces Huntington’s disease-like neuronal dysfunction. Mol Neurodegener 4:11PubMedCentralPubMedGoogle Scholar
  268. Wexler NS, Lorimer J, Porter J, Gomez F, Moskowitz C, Shackell E, Marder K, Penchaszadeh G, Roberts SA, Gayan J, Brocklebank D, Cherny SS, Cardon LR, Gray J, Dlouhy SR, Wiktorski S, Hodes ME, Conneally PM, Penney JB, Gusella J, Cha JH, Irizarry M, Rosas D, Hersch S, Hollingsworth Z, MacDonald M, Young AB, Andresen JM, Housman DE, De Young MM, Bonilla E, Stillings T, Negrette A, Snodgrass SR, Martinez-Jaurrieta MD, Ramos-Arroyo MA, Bickham J, Ramos JS, Marshall F, Shoulson I, Rey GJ, Feigin A, Arnheim N, Acevedo-Cruz A, Acosta L, Alvir J, Fischbeck K, Thompson LM, Young A, Dure L, O’Brien CJ, Paulsen J, Brickman A, Krch D, Peery S, Hogarth P, Higgins DS Jr, Landwehrmeyer B (2004) Venezuelan kindreds reveal that genetic and environmental factors modulate Huntington’s disease age of onset. Proc Natl Acad Sci U S A 101(10):3498–3503PubMedCentralPubMedGoogle Scholar
  269. White JK, Auerbach W, Duyao MP, Vonsattel JP, Gusella JF, Joyner AL, MacDonald ME (1997) Huntingtin is required for neurogenesis and is not impaired by the Huntington’s disease CAG expansion. Nat Genet 17(4):404–410PubMedGoogle Scholar
  270. Whitehouse PJ, Trifiletti RR, Jones BE, Folstein S, Price DL, Snyder SH, Kuhar MJ (1985) Neurotransmitter receptor alterations in Huntington’s disease: autoradiographic and homogenate studies with special reference to benzodiazepine receptor complexes. Ann Neurol 18(2):202–210PubMedGoogle Scholar
  271. Witjes-Ane MN, Zwinderman AH, Tibben A, van Ommen GJ, Roos RA (2002) Behavioural complaints in participants who underwent predictive testing for Huntington’s disease. J Med Genet 39(11):857–862PubMedCentralPubMedGoogle Scholar
  272. Yamamoto A, Lucas JJ, Hen R (2000) Reversal of neuropathology and motor dysfunction in a conditional model of Huntington’s disease. Cell 101(1):57–66PubMedGoogle Scholar
  273. Yohrling GJ, Jiang GC, DeJohn MM, Miller DW, Young AB, Vrana KE, Cha JH (2003) Analysis of cellular, transgenic and human models of Huntington’s disease reveals tyrosine hydroxylase alterations and substantia nigra neuropathology. Brain Res Mol Brain Res 119 (1):28–36Google Scholar
  274. Young AB, Greenamyre JT, Hollingsworth Z, Albin R, D’Amato C, Shoulson I, Penney JB (1988) NMDA receptor losses in putamen from patients with Huntington’s disease. Science 241(4868):981–983PubMedGoogle Scholar
  275. Yung KK, Smith AD, Levey AI, Bolam JP (1996) Synaptic connections between spiny neurons of the direct and indirect pathways in the neostriatum of the rat: evidence from dopamine receptor and neuropeptide immunostaining. Eur J Neurosci 8(5):861–869PubMedGoogle Scholar
  276. Zappacosta B, Monza D, Meoni C, Austoni L, Soliveri P, Gellera C, Alberti R, Mantero M, Penati G, Caraceni T, Girotti F (1996) Psychiatric symptoms do not correlate with cognitive decline, motor symptoms, or CAG repeat length in Huntington’s disease. Arch Neurol 53(6):493–497PubMedGoogle Scholar
  277. Zeitlin S, Liu JP, Chapman DL, Papaioannou VE, Efstratiadis A (1995) Increased apoptosis and early embryonic lethality in mice nullizygous for the Huntington’s disease gene homologue. Nat Genet 11(2):155–163PubMedGoogle Scholar
  278. Zuccato C, Cattaneo E (2007) Role of brain-derived neurotrophic factor in Huntington’s disease. Prog Neurobiol 81(5–6):294–330PubMedGoogle Scholar
  279. Zuccato C, Ciammola A, Rigamonti D, Leavitt BR, Goffredo D, Conti L, MacDonald ME, Friedlander RM, Silani V, Hayden MR, Timmusk T, Sipione S, Cattaneo E (2001) Loss of huntingtin-mediated BDNF gene transcription in Huntington’s disease. Science 293(5529):493–498PubMedGoogle Scholar
  280. Zuccato C, Tartari M, Crotti A, Goffredo D, Valenza M, Conti L, Cataudella T, Leavitt BR, Hayden MR, Timmusk T, Rigamonti D, Cattaneo E (2003) Huntingtin interacts with REST/NRSF to modulate the transcription of NRSE-controlled neuronal genes. Nat Genet 35(1):76–83PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Henry J. Waldvogel
    • 1
    Email author
  • Eric H. Kim
    • 1
  • Lynette J. Tippett
    • 3
  • Jean-Paul G. Vonsattel
    • 2
  • Richard LM Faull
    • 1
  1. 1.Centre for Brain Research, Department of Anatomy with RadiologyUniversity of AucklandAucklandNew Zealand
  2. 2.Department of Pathology, Presbyterian HospitalColumbia UniversityNew YorkUSA
  3. 3.Centre for Brain Research, Department of PsychologyUniversity of AucklandAucklandNew Zealand

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