Journal of Neural Transmission

, Volume 103, Issue 4, pp 455–490

Pattern of brain destruction in Parkinson's and Alzheimer's diseases

  • H. Braak
  • E. Braak
  • D. Yilmazer
  • R. A. I. de Vos
  • E. N. H. Jansen
  • J. Bohl
Alzheimer's Disease and Related Disorders

Summary

Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common age-related degenerative disorders of the human brain. Both diseases involve multiple neuronal systems and are the consequences of cytoskeletal abnormalities which gradually develop in only a small number of neuronal types. In AD, susceptible neurons produce neurofibrillary tangles (NFTs) and neuropil threads (NTs), while in PD, they develop Lewy bodies (LBs) and Lewy neurites (LNs). The specific lesional pattern of both illnesses accrues slowly over time and remains remarkably consistent across cases.

In AD, six developmental stages can be distinguished on account of the predictable manner in which the neurofibrillary changes spread across the cerebral cortex. The pathologic process commences in the transentorhinal region (clinically silent stages I and II), then proceeds into adjoining cortical and subcortical components of the limbic system (stages III and IV — incipient AD), and eventually extends into association areas of the neocortex (stages V and VI — fully developed AD).

During the course of PD, important components of the limbic system undergo specific lesions as well. The predilection sites include the entorhinal region, the CA2-sector of the hippocampal formation, the limbic nuclei of the thalamus, anterior cingulate areas, agranular insular cortex (layer VI), and — within the amygdala — the accessory cortical nucleus, the ventromedial divisions both of the basal and accessory basal nuclei, and the central nucleus. The amygdala not only generates important projections to the prefrental association areas but also exerts influence upon all non-thalamic nuclei which in a non-specific manner project upon the cerebral cortex and upon the nuclei regulating endocrine and autonomie functions. All these amygdala-dependent structures themselves exhibit severe PD-specific lesions. In general, the extranigral destructions are in themselves not sufficient to produce overt intellectual deterioration. Similarly, AD-related pathology up to stage III may be asymptomatic as well. Fully developed PD with concurring incipient AD, however, is likely to cause impaired cognition. Presently available data support the view that the occurrence of additional lesions in the form of AD stage III (or more) destruction is the most common cause of intellectual decline in PD.

Keywords

Alzheimer's disease Parkinson's disease limbic system neurofibrillary changes Lewy bodies Lewy neurite 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Agid Y, Ruberg M, Javoy-Agid F, Hirsch E, Raisman-Vozari R, Vyas S, Faucheux B, Michel P, Kastner A, Blanchard V, Dier P, Villares J, Zhang P (1993) Are dopamin ergic neurons selectively vulnerable to Parkinson's disease? Adv Neurol 60: 148–164Google Scholar
  2. Airaksinen MS, Paer A, Paljärvi L, Reinikanen K, Riekkinen P, Suomalainen R, Panula P (1991) Histamine neurons in human hypothalamus: anatomy in normal and Alzheimer diseased brains. Neuroscience 44: 465–481Google Scholar
  3. Alheid GF, Heimer L, Switzer RC (1990) Basal ganglia. In: Paxinos G (ed) The human nervous system. Academic Press, New York, pp 483–582Google Scholar
  4. Alexander GE, Crutcher MD, DeLong MR (1990) Basal ganglia-thalamocortical circuits: parallel substrates for motor, oculomotor, “prefrontal” and “limbic” functions. Progr Brain Res 85: 119–146Google Scholar
  5. Amaral DG (1987) Memory: anatomical organization of candidate brain regions. In: Brookhart JM, Mountcastle VB (eds) Handbook of physiology: the nervous system, V. Higher function of the nervous system, 5th ed. Am Physiol Soc, Bethesda, pp 211–294Google Scholar
  6. Amaral DG, Witter MP (1989) The three-dimensional organization of the hippocampal formation: a review of anatomical data. Neuroscience 31: 571–591Google Scholar
  7. Amaral DG, Insausti R (1990) Hippocampal formation. In: Paxinos G (ed) The human nervous system. Academic Press, San Diego, pp 711–755Google Scholar
  8. Amaral DG, Price JL, Pitkänen A, Carmichael ST (1992) Anatomical organization of the primate amygdaloid complex. In: Aggleton JP (ed) The amygdala: neurobiological aspects of emotion, memory, and mental dysfunction. Wiley-Liss, New York, pp 1–66Google Scholar
  9. Arendt T, Bigl V, Arendt A, Tennstedt A (1983) Loss of neurones in nucleus basalis of Meynert in Alzheimer's disease, paralysis agitans and Korsakoff s disease. Acta Neuropathol 61: 101–108Google Scholar
  10. Armstrong E (1990) Limbic thalamus: anterior and mediodorsal nuclei. In: Paxinos G (ed) The human nervous system. Academic Press, San Diego, pp 469–482Google Scholar
  11. Arnold SE, Hyman BT, Flory J, Damasio AR, van Hoesen GW (1991) The topographical and neuroanatomical distribution of neurofibrillary tangles and neuritic plaques in the cerebral cortex of patients with Alzheimer's disease. Cerebral Cortex 1: 103–116Google Scholar
  12. Babinski R, Calabrese P, Durwen HF, Markowitsch HJ, Brechtelsbauer D, Heuser L, Gehlen W (1993) The possible contribution of the amygdala to memory. Behav Neurol 6: 167–170Google Scholar
  13. Bancher C, Brunner C, Lassmann H, Budka H, Jellinger K, Wiche G, Scitelberger F, Grundke-Iqbal I, Wisniewski HM (1989) Accumulation of abnormally phosphorylated τ precedes the formation of neurofibrillary tangles in Alzheimer's disease. Brain Res 477: 90–99Google Scholar
  14. Bancher C, Braak H, Fischer P, Jellinger KA (1993) Neuropathological staging of Alzheimer lesions and intellectual status in Alzheimer's and Parkinson's disease. Neurosci Lett 162: 179–182Google Scholar
  15. Braak E, Braak H, Mandelkow EM (1994) A sequence of cytoskeleton changes related to the formation of neurofibrillary tangles and neuropil threads. Acta Neuropathol 87: 554–567Google Scholar
  16. Braak H (1980) Architectonics of the human telencephalic cortex. Springer, Berlin Heidelberg New York, pp 1–147Google Scholar
  17. Braak H, Braak E (1983) Neuronal types in the basolateral amygdaloid nuclei of man. Brain Res Bull 11: 349–365Google Scholar
  18. Braak H, Braak E (1985) On areas of transition between entorhinal allocortex and temporal isocortex in the human brain. Normal morphology and lamina-specific pathology in Alzheimer's disease. Acta Neuropathol 68: 325–332Google Scholar
  19. Braak H, Braak E (1986) Nuclear configuration and neuronal types of the nucleus niger in the brain of the human adult. Hum Neurobiol 5: 71–82Google Scholar
  20. Braak H, Braak E (1989) Cortical and subcortical argyrophilic grains characterize a disease associated with adult onset dementia. Neuropathol Appl Neurobiol 15: 13–26Google Scholar
  21. Braak H, Braak E (1990) Cognitive impairment in Parkinson's disease: amyloid plaques, neurofibrillary tangles and neuropil threads in the cerebral cortex. J Neural Transm [P-D Sect] 2: 45–57Google Scholar
  22. Braak H, Braak E (1991a) Alzheimer's disease affects limbic nuclei of the thalamus. Acta Neuropathol 81: 261–268Google Scholar
  23. Braak H, Braak E. (1991b) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82: 239–259Google Scholar
  24. Braak H, Braak E (1992a) Anatomy of the human hypothalamus (chiasmatic and tuberal region). Progr Brain Res 93: 3–16Google Scholar
  25. Braak H, Braak E (1992b) The human entorhinal cortex: normal morphology and lamina-specific pathology in various diseases. Neurosci Res 15: 6–31Google Scholar
  26. Braak H, Braak E (1993a) Alzheimer neuropathology and limbic circuits. In: Vogt BA, Gabriel M (eds) Neurobiology of cingulate cortex and limbic thalamus. Birkhäuser, Boston, pp 606–626Google Scholar
  27. Braak H, Braak E (1993b) Anatomy of the human basal ganglia. In: Szelenyi I (ed) Inhibitors of monoamine oxidase B. Birkhäuser, Basel, pp 3–23Google Scholar
  28. Braak H, Braak E (1994) Pathology of Alzheimer's disease. In: Calne DB (ed) Neurodegenerative diseases. Saunders, Philadelphia, pp 585–613Google Scholar
  29. Braak H, Braak E (1995) Staging of Alzheimer related neurofibrillary changes. Neurobiol Aging 16: 271–284Google Scholar
  30. Braak H, Braak E, Bohl J (1992) Retrosplenial region involvement in Alzheimer's disease. Neurodegeneration 1: 53–57Google Scholar
  31. Braak H, Duyckaerts C, Braak E, Piette F (1993) Neuropathological staging of Alzheimer-related changes correlates with psychometrically assessed intellectual status. In: Corian B, Iqbal K, Nicolini M, Winblad B, Wisniewski H, Zatta PF (eds) Alzheimer's disaese: advances in clinical and basic research. Wiley, Chichester, pp 131–137Google Scholar
  32. Braak H, Braak E, Yilmazer D, de Vos RAI, Jansen ENH, Bohl J, Jellinger K (1994) Amygdala pathology in Parkinson's disease. Acta Neuropathol 88: 493–500Google Scholar
  33. Braak H, Braak E, Yilmazer D, de Vos RAI, Jansen ENH, Bohl J, Jellinger K (1995) Nigral and extranigral lesions in Parkinson's disease. J Neural Transm [Suppl] 46: 15–31Google Scholar
  34. Braak H, Braak E, Yilmazer D, Bohl J (1996) Functional anatomy of the human hippocampal formation. Review. J Child Neurol (in press)Google Scholar
  35. Calne DB (1983) Current views on Parkinson's disease. Can J Neurol Sci 10: 11–15Google Scholar
  36. Chan-Palay V, Asan E (1989) Alterations in catecholamine neurons of the locus coeruleus in senile dementia of the Alzheimer type and in Parkinson's disease with and without dementia and depression. J Comp Neurol 287: 373–392Google Scholar
  37. Damasio AR, Damasio H (1991) Disorders of higher brain function. In: Rosenberg RN (ed) Comprehensive neurology. Raven Press, New York, pp 639–657Google Scholar
  38. DeLacalle S, Lim C, Sobreviela T, Mufson EJ, Hersh LB, Saper CP (1994) Cholinergic innervation in the human hippocampal formation including the entorhinal cortex. J Comp Neurol 345: 321–344Google Scholar
  39. De Olmos J (1990) Amygdala. In: Paxinos G (ed) The human nervous system. Academic Press, New York, pp 583–710Google Scholar
  40. De Vos RAI, Jansen ENH, Stam FC, Ravid R, Swaab D (1995) “Lewy body disease”: clinico-pathological correlations in 18 consecutive cases of Parkinson's disease with and without dementia. Clin Neurol Neurosurg 97: 13–22Google Scholar
  41. Dickson DW, Ruan D, Crystal H, Mark MH, Davies P, Kress Y, Yen SH (1991) Hippocampal degeneration differentiates diffuse Lewy body disease (DLBD) from Alzheimer's disease: light and electron microscopic immunocytochemistry of CA2-3 neuntes specific to DLBD. Neurology 41: 1402–1409Google Scholar
  42. Fearnley J, Lees A (1994) Pathology of Parkinson's disease. In: Calne DB (ed) Neurodegenerative diseases. Saunders, Philadelphia, pp 545–554Google Scholar
  43. Felleman DJ, van Essen DC (1991) Distributed hierarchical processing in the primate cerebral cortex. Cerebral Cortex 1: 1–47Google Scholar
  44. Forno LS (1986) The Lewy body in Parkinson's disease. Adv Neurol 45: 35–43Google Scholar
  45. Galloway PG, Grundke-Iqbal I, Iqbal K, Perry G (1988) Lewy bodies contain epitopes both shared and distinct from Alzheimer neurofibrillary tangles. J Neuropathol Exp Neurol 47: 654–663Google Scholar
  46. German DC, White CL, Sparkman DR (1987) Alzheimer's disease: neurofibrillary tangles in nuclei that project to the cerebral cortex. Neuroscience 21: 305–312Google Scholar
  47. Gibb WRG (1989) The pathology of parkinsonian disorders. In: Quinn NP, Jenner PG (eds) Disorders of movement — clinical, pharmacological and physiological aspects. Academic Press, London, pp 33–57Google Scholar
  48. Gibb WRG, Lees AJ (1988) The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease. J Neurol Neurosurg Psychiatry 51: 745–752Google Scholar
  49. Gibb WRG, Lees AJ (1989) The significance of the Lewy body in the diagnosis of idiopathic Parkinson's disease. Neuropathol Appl Neurobiol 15: 27–44Google Scholar
  50. Gibb WRG, Lees AJ (1991) Anatomy, pigmentation, ventral and dorsal subpopulations of the substantia nigra, and differential cell death in Parkinson's disease. J Neurol Neurosurg Psychiatry 54: 388–396Google Scholar
  51. Gibb WRG, Scott T, Lees AJ (1991) Neuronal inclusions of Parkinson's disease. Mov Disord 6: 2–11Google Scholar
  52. Goedert M (1993) Tau protein and the neurofibrillary pathology of Alzheimer's disease. Trends Neurosci 16: 460–465Google Scholar
  53. Goldman-Rakic PS (1987) Circuitry of primate prefrontal cortex and regulation of behavior by representational memory. In: Brookhart JM, Mountcastle VB (eds) Handbook of physiology: the nervous system, V. Higher functions of the nervous system, 5th ed. Am Physiol Soc, Bethesda, pp 373–407Google Scholar
  54. Goldman-Rakic PS, Porrino LJ (1985) The primate mediodorsal (MD) nucleus and its projections to the frontal lobe. J Comp Neurol 242: 535–560Google Scholar
  55. Hedreen JC, Struble RG, Whitehouse PJ, Price DL (1984) Topography of the magnocellular basal forebrain system in human brain. J Neuropathol Exp Neurol 31: 1–21Google Scholar
  56. Heimer L, Switzer RC, van Hoesen GW (1982) Ventral striatum and ventral pallidum. Components of the motor system? Trends Neurosci 5: 83–87Google Scholar
  57. Heimer L, de Olmos J, Alheid GF, Zaborszky L (1991) “Perestroika” in the basal forebrain: opening the border between neurology and psychiatry. Progr Brain Res 87: 109–165Google Scholar
  58. Herzog AG, Kemper TL (1980) Amygdaloid changes in aging and dementia. Arch Neurol 7: 625–629Google Scholar
  59. Hirsch EC, Graybiel AM, Agid YA (1988) Melanized dopaminergic neurons are differently susceptible to degeneration in Parkinson's disease. Nature 334: 345–348Google Scholar
  60. Hyman BT, van Hoesen GW, Damasio AR, Barnes CL (1984) Alzheimer's disease: cellspecific pathology isolates the hippocampal formation. Science 225: 1168–1170Google Scholar
  61. Hyman BT, van Hoesen GW, Damasio AR (1990) Memory-related neural systems in Alzheimer's disease: an anatomic study. Neurology 40: 1721–1730Google Scholar
  62. Insausti R, Tunon T, Sobreviela T, Insausti AM, Gonzalo LM (1995) The human entorhinal cortex: a cytoarchitectonic analysis. J Comp Neurol 335: 171–198.Google Scholar
  63. Iqbal K, Alonso AC, Gong CX, Khatoon S, Singh TJ, Grundke-Iqbal I (1994) Mechanism of neurofibrillary degeneration in Alzheimer's disease. Mol Neurobiol 9: 119–123Google Scholar
  64. Jellinger K (1989) Pathology of Parkinson's disease. In: Calne DB (ed) Handbook of experimental pharmacology, vol 88. Drugs for the treatment of Parkinson's disease. Springer, Berlin Heidelberg New York Tokyo, pp 44–112Google Scholar
  65. Jellinger K (1991) Pathology of Parkinson's disease. Changes other than the nigrostriatal pathway. Mol Chem Neuropathol 14: 153–197Google Scholar
  66. Jellinger K (1994) Structural basis of dementia in Parkinson's disease. In: Korczyn AD (ed) Dementia in Parkinson's disease. Monduzzi, Bologna, pp 31–38Google Scholar
  67. Jellinger K, Bancher C (1995) Structural basis of mental impairment in Parkinson's disease. Neuropsychiatrie 9: 9–14Google Scholar
  68. Jellinger K, Braak H, Braak E, Fischer P (1991) Alzheimer lesions in the entorhinal region and isocortex in Parkinson's and Alzheimer's diseases. Ann NY Acad Sci 640: 203–209Google Scholar
  69. Jones EG (1985) The thalamus. Plenum, New YorkGoogle Scholar
  70. Kalus P, Braak H, Braak E, Bohl J (1989) The presubicular region in Alzheimer's disease: topography of amyloid deposits and neurofibrillary changes. Brain Res 494: 198–203Google Scholar
  71. Kemper TL (1978) Senile dementia: a focal disease in the temporal lobe. In: Nandy E (ed) Senile dementia: a biomedical approach. Elsevier, Amsterdam, pp 105–113Google Scholar
  72. Kromer-Vogt LJ, Hyman BT, van Hoesen GW, Damasio AR (1990) Pathologic alterations in the amygdala in Alzheimer's disease. Neuroscience 37: 377–385Google Scholar
  73. Langston JW, Forno LS (1978) The hypothalamus in Parkinson's disease. Ann Neurol 3: 129–133Google Scholar
  74. Lewy FH (1923) Die Lehre vom Tonus der Bewegung, zugleich systematische Untersuchungen zur Klinik, Physiologie, Pathologie und Pathogenese der Paralysis agitans. Springer, BerlinGoogle Scholar
  75. Lowe J (1994) Lewy bodies. In: Calne DB (ed) Neurodegenerative diseases. Saunders, Philadelphia, pp 51–69Google Scholar
  76. Manaye KF, McIntire DD, Mann DMA, German DC (1995) Locus coeruleus cell loss in the aging human brain: a non-random process. J Comp Neurol 358: 79–87Google Scholar
  77. Mann DMA (1984) Dopamine neurones of the vertebrate brain: some aspects of anatomy and pathology. In: Winslow W, Markstein R (eds) The neurobiology of dopamine systems. Univers Press, Manchester, pp 87–103Google Scholar
  78. Marinkovic SV, Milisavljevic MM, Vuckovic VD (1991) Microvascular anatomy of the uncus and the parahippocampal gyrus. Neurosurgery 29: 805–814Google Scholar
  79. Markowitsch HJ (1982) Thalamic mediodorsal nucleus and memory: a critical evaluation of studies in animals and man. Neurosci Biobehav Rev 6: 351–380Google Scholar
  80. Markowitsch HJ (1995) Anatomical basis of memory disorders. In: Gazzaniga MS (ed) The cognitive neurosciences. MIT Press, Cambridge, Mass, pp 765–779Google Scholar
  81. Matzuk MM, Saper CB (1985) Preservation of hypothalamic dopaminergic neurons in Parkinson's disease. Ann Neurol 18: 552–555Google Scholar
  82. Mesulam MM, Geula C (1988) Nucleus basalis (DH4) and cortical cholinergic innervation in the human brain: observations based on the distribution of acetylcholinestease and choline acetyltransferase. J Comp Neurol 275: 216–240Google Scholar
  83. Mesulam MM, Hersh LB, Mash DC, Geula C (1992) Differential cholinergic innervation within functional subdivisions of the human cerebral cortex — a choline acetyltransferase study. J Comp Neurol 318: 316–328Google Scholar
  84. Mishkin M (1982) A memory system in the monkey. Phil Trans R Soc London B 298: 85–95Google Scholar
  85. Mizutani T, Kasahara M (1995) Degeneration of the intrahippocampal routes of the perforant and alvear pathways in senile dementia of Alzheimer type. Neurosci Lett 184: 141–144Google Scholar
  86. Moossy J, Zubenko GS, Martinez AJ, Rao GR (1988) Bilateral symmetry of morphological lesions in Alzheimer's disease. Arch Neurol 45: 251–254Google Scholar
  87. Nakano I, Hirano A (1984) Parkinson's disease: neuron loss in the nucleus basalis without concomitant Alzheimer's disease. Ann Neurol15: 415–418Google Scholar
  88. Nauta HJW (1979) A proposed conceptual reorganization of the basal ganglia and telencephalon. Neuroscience 4: 1875–1881Google Scholar
  89. Nauta WJH (1986) Circuitous connections linking cerebral cortex, limbic system, and corpus striatum. In: Doane BK, Livingston KE (eds) The limbic system. Raven Press, New York, pp 43–54Google Scholar
  90. Ohm TG, Braak H (1988) The pigmented subpeduncular nucleus: a neuromelanin-containing nucleus in the human pontine tegmentum. Morphology and changes in Alzheimer's disease. Acta Neuropathol 77: 26–32Google Scholar
  91. Ohm TG, Heilmann R, Braak H (1989) The human oral raphe system. Architectonics and neuronal types in pigment-Nissl preparations. Anat Embryol 180: 37–43Google Scholar
  92. Pandya DN, Yeterian (1985) Architecture and connections of cortical association areas. In: Peters A, Jones EG (eds) Cerebral cortex, vol 4. Association and auditory cortices. Plenum Press, New York, pp 3–61Google Scholar
  93. Pandya DN, Yeterian EH (1990) Prefrontal cortex in relation to other cortical areas in rhesus monkey: architecture and connections. Progr Brain Res 85: 63–94Google Scholar
  94. Panula P, Airaksinen MS, Pirvola U, Kotilainen E (1990) A histamin-containing neuronal system in human brain. Neuroscience 34: 127–132Google Scholar
  95. Paulus W, Jellinger K (1991) The neuropathologic basis of different clinical subgroups of Parkinson's disease. J Neuropathol Exp Neurol 50: 743–755Google Scholar
  96. Pearson J, Halliday G, Sakamoto N, Michel JP (1990) Catecholaminergic neurons. In: Paxinos G (ed) The human nervous system. Academic Press, New York, pp 1023–1050Google Scholar
  97. Price JL, Russchen FT, Amaral DG (1987) The amygdaloid complex. In: Björklund A, Hökfelt T, Swansen LW (eds) Handbook of chemical neuroanatomy, vol 5, part I. Integrated systems. Elsevier, Amsterdam, pp 279–388Google Scholar
  98. Price JL, Davis PB, Morris JC, White DL (1991) The distribution of tangles, plaques and related immunohistochemical markers in healthy aging and Alzheimer's disease. Neurobiol Aging 12: 295–312Google Scholar
  99. Rosene DL, van Hoesen GW (1987) The hippocampal formation of the primate brain. A review of some comparative aspects of cytoarchitecture and connections. In: Jones EG, Peters A (eds) Cerebral cortex, vol 6. Further aspects of cortical functions including hippocampus. Plenum Press, New York, pp 345–456Google Scholar
  100. Saper CB (1987a) Function of the locus coeruleus. Trends Neurosci 10: 343–344Google Scholar
  101. Saper CB (1987b) Diffuse cortical projection systems: anatomical organization and role in cortical function. In: Plum F (ed) Handbook of physiology, vol 5. The nervous system. Am Physiol Soc, Bethesda, pp 169–210Google Scholar
  102. Saper CB (1990a) Hypothalamus. In: Paxinos G (ed) The human nervous system. Academic Press, New York, pp 389–413Google Scholar
  103. Saper CB (1990b) Cholinergic system. In: Paxinos G (ed) The human nervous system. Academic Press, New York, pp 1095–1113Google Scholar
  104. Saper CB, Chelimsky TC (1984) A cytoarchitectonic and histochemical study of nucleus basalis and associated cell groups in the normal human brain. Neuroscience 13: 1023–1037Google Scholar
  105. Saper CB, German DC (1987) Hypothalamic pathology in Alzheimer's disease. Neurosci Lett 74: 364–370Google Scholar
  106. Saper CB, German DC, White CL (1985) Neuronal pathology in the nucleus basalis and associated cell groups in senile dementia of the Alzheimer's type: possible role in cell loss. Neurology 35: 1089–1095Google Scholar
  107. Squire LR, Zola-Morgan S (1988) Memory: brain systems and behavior. Trends Neurosci 11: 170–175Google Scholar
  108. Squire LR, Zola-Morgan S (1991) The medial temporal lobe memory system. Science 253: 1380–1386Google Scholar
  109. Stephan H (1975) Allocortex. In: Bargmann W (ed) Handbuch der mikroskopischen Anatomie des Menschen, vol 4/9. Springer, Berlin Heidelberg New YorkGoogle Scholar
  110. Swaab DF, Grundke-Iqbal I, Iqbal K, Kremer HPH, Ravid R, van de Nes JAP (1992) Tau and ubiquitin in the human hypothalamus in aging and Alzheimer's disease. Brain Res 590: 239–249Google Scholar
  111. Törk I, Hornung JP (1990) Raphe nuclei and the serotonergic system. In: Paxinos G (ed) The human nervous system. Academic Press, New York, pp 1001–1022Google Scholar
  112. Tourtellotte WG, van Hoesen GW, Hyman BT, Tikoo RK, Damasio AR (1989) Alz-50 immunoreactivity in the thalamic reticular nucleus in Alzheimer's disease. Brain Res 515: 227–234Google Scholar
  113. Unger JW, McNeill TH, Lapham LL, Hamill RW (1988) Neuropeptides and neuropathology in the amygdala in Alzheimer's disease: relationship between somatostatin, neuropeptide Y and subregional distribution of neuritic plaques. Brain Res 452: 293–302Google Scholar
  114. van Domburg PHMF, ten Donkelaar HJ (1991) The human substantia nigra and ventral tegmental area. In: Beck F, Hild W, Kriz W, Pauly JE, Sano Y, Schiebler TH (eds) Advances in anatomy, embryology and cell biology, vol 121. Springer, Berlin Heidelberg New York TokyoGoogle Scholar
  115. van Dongen PAM (1981) The human locus coeruleus in neurology and psychiatry. Progr Neurobiol 17: 97–139Google Scholar
  116. van Hoesen GW, Hyman BT (1990) Hippocampal formation: anatomy and the patterns of pathology in Alzheimer's disease. Progr Brain Res 83: 445–457Google Scholar
  117. van Hoesen GW, Hyman BT, Damasio AR (1991) Entorhinal cortex pathology in Alzheimer's disease. Hippocampus 1: 1–8Google Scholar
  118. van Hoesen GW, Solodkin A (1993) Some modular features of temporal cortex in humans as revealed by pathological changes in Alzheimer's disease. Cerebral Cortex 3: 465–475Google Scholar
  119. Vogt BA (1985) Cingulate cortex. In: Peters A, Jones EG (eds) Cerebral cortex, vol 4. Association and auditory cortices. Plenum Press, New York, pp 89–149Google Scholar
  120. Whitehouse PJ, Hedreen JC, White CL, Price DL (1983) Basal forebrain neurons in the dementia of Parkinson's disease. Ann Neurol 13: 243–248Google Scholar
  121. Witter MP (1993) Organization of the entorhinal-hippocampal system: a review of current anatomical data. Hippocampus 3: 33–44Google Scholar
  122. Xuereb JH, Perry EK, Candy JM, Bonham JR, Perry RH, Marshall E (1990) Parameters of cholinergic neurotransmission in the thalamus in Parkinson's disease and Alzheimer's disease. J Neurol Sci 99: 185–197Google Scholar
  123. Zilles K (1990) Cortex. In: Paxinos G (ed) The human nervous system. Academic Press, New York, pp 757–802Google Scholar
  124. Zola-Morgan S, Squire LR (1993) Neuroanatomy of memory. Ann Rev Neurosci 16: 547–563Google Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • H. Braak
    • 1
  • E. Braak
    • 1
  • D. Yilmazer
    • 1
  • R. A. I. de Vos
    • 2
  • E. N. H. Jansen
    • 2
  • J. Bohl
    • 3
  1. 1.Zentrum der MorphologieJ.W. Goethe UniversitätFrankfurt/MainFederal Republic of Germany
  2. 2.Streeklaboratoria voor pathologieBurg. Edo bergsmalaanEnschedeThe Netherlands
  3. 3.Abteilung für NeuropathologieJ. Gutenberg UniversitätMainzFederal Republic of Germany

Personalised recommendations