Skip to main content
SpringerLink
Log in

Classical and Modern Neuropathological Approaches to Alzheimer’s Disease

  • Conference paper
Neurology

  • 165 Accesses

Abstract

Alzheimer’s disease (AD), the most common type of adult-onset dementia [65], has been analyzed at several levels (Table 1; Fig. 1): regional distributions of disease; neuronal populations/systems at risk; abnormalities occurring in individual nerve cells; and molecular pathology of cellular constituents. These investigations have demonstrated that AD selectively involves specific parts of brain, certain transmitter systems, and components of the neuronal cytoskeleton. Dysfunction/death of at-risk populations of neurons in brainstem, basal forebrain, amygdala, hippocampus, and neocortex leads to impairments in memory, language, visual-spatial perceptions, etc. Human studies are complemented by investigations in animals that are essential for analyzing mechanisms, evolutions, and consequences of disorders in certain neuronal populations, for studying the cellular and molecular dynamics of disease processes, and for relating these processes to the clinical expressions of illness. This review discusses some new information derived from neuropathological and neurobiological studies of AD and of animal models sharing features with the human disease (Table 1; Fig. 1).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Aigner T, Aggleton J, Mitchell SJ, Price D, DeLong M, Mishkin M (1983) Effects of scopolamine on recognition memory in monkeys after ibotenic acid injections into the nucleus basalis of Meynert. Soc Neurosci Abstr 9: 826

    Google Scholar 

  2. Aigner T, Mitchell S, Aggleton J, DeLong M, Struble R, Wenk G, Price D, Mishkin M (1984) Recognition deficit in monkeys following neurotoxic lesions of the basal forebrain. Soc Neurosci Abstr 10: 386

    Google Scholar 

  3. Anderton BH, Breinburg D, Downes MJ, Green PJ, Tomlinson BE, Ulrich J, Wood JN, Kahn J (1982) Monoclonal antibodies show that neurofibrillary tangles and neurofilaments share antigenic determinants. Nature 298: 84–86

    Article  PubMed  CAS  Google Scholar 

  4. Arendt T, Bigl V, Arendt A, Tennstedt A (1983) Loss of neurons in the nucleus basalis of Meynert in Alzheimer’s disease, paralysis agitans, and Korsakoff’s disease. Acta Neuropathol(Berl) 61: 101–108

    Article  CAS  Google Scholar 

  5. Ball MJ (1977) Neuronal loss, neurofibrillary tangles and granulovacuolar degeneration in the hippocampus with ageing and dementia. A qualitative study. Acta Neuropathol (Berl) 37: 111 – 118

    Article  CAS  Google Scholar 

  6. Bartus RT, Dean RL III, Beer B, Lippa AS (1982) The cholinergic hypothesis of geriatric memory dysfunction. Science 217: 408–417

    Article  PubMed  CAS  Google Scholar 

  7. Beal MF, Mazurek MF, Tran VT, Chattha G, Bird ED, Martin JB (1985) Reduced numbers of somatostatin receptors in the cerebral cortex in Alzheimer’s disease. Science 229: 289–291

    Article  PubMed  CAS  Google Scholar 

  8. Bizzi A, Crane RC, Autilio-Gambetti L, Gambetti P (1984) Aluminum effect on slow axonal transport: a novel impairment of neurofilament transport. J Neurosci 4: 722–731

    PubMed  CAS  Google Scholar 

  9. BondareffW, Mountjoy CQ, Roth M (1982) Loss of neurons or origin of the adrenergic projection to cerebral cortex (nucleus locus ceruleus) in senile dementia. Neurology 32: 164–168

    PubMed  CAS  Google Scholar 

  10. Bowen DM (1983) Biochemical assessment of neurotransmitter and metabolic dysfunction and cerebral atrophy in Alzheimer’s disease. Biological aspects of Alzheimer’s Disease. Banbury Rep 15: 219–231

    Google Scholar 

  11. Brun A (1983) An overview of light and electron microscopic changes. In: Reisberg B (ed) Alzheimer’s disease. The Free Press, New York, pp 37–47

    Google Scholar 

  12. Buell SJ, Coleman PD (1981) Quantitative evidence for selective dendritic growth in normal human aging but not in senile dementia. Brain Res 214: 23–41

    Article  PubMed  CAS  Google Scholar 

  13. Cleveland DW, Sullivan KF (1985) Molecular biology and genetics of tubulin. Annu Rev Biochem 54: 331–365

    Article  PubMed  CAS  Google Scholar 

  14. Colon EJ (1973) The cerebral cortex in presenil dementia. A quantitative analysis. Acta Neuropathol (Berl) 23: 281–290

    Article  CAS  Google Scholar 

  15. Cork LC, Altschuler RJ, Struble RG, Casanova MF, Price DL, Sternberger N, Sternberger L (1985) Changes in the distribution of phosphorylated neurofilaments in Alzheimer’s disease. J Neuropathol Exp Neurol 44: 368

    Article  Google Scholar 

  16. Cork LC, Sternberger NH, Sternberger LA, Casanova MF, Struble RG, Price DL (1986) Phosphorylated neurofilament antigens in neurofibrillary tangles in Alzheimer’s disease. J Neuropathol Exp Neurol

    Google Scholar 

  17. Coyle JT, Price DL, DeLong MR (1983) Alzheimer’s disease: a disorder of cortical cholinergic innervation. Science 219: 1184–1190

    Article  PubMed  CAS  Google Scholar 

  18. Cross AJ, Crow TJ, Perry EK, Perry RH, Blessed G, Tomlinson BE (1981) Reduced dopamine-ß-hydroxylase activity in Alzheimer’s disease. Br Med J 282: 93–94

    Article  CAS  Google Scholar 

  19. Davies P, Katzman R, Terry RD (1980) Reduced somatostatin-like immunoreactivity in cerebral cortex from cases of Alzheimer disease and Alzheimer senile dementia. Nature 288: 279–280

    Article  PubMed  CAS  Google Scholar 

  20. Davis RT(1978) Old monkey behavior. Exp Gerontol 13:237–250

    Article  PubMed  CAS  Google Scholar 

  21. Gambetti P, Shecket G, Ghetti B, Hirano A, Dahl D (1983) Neurofibrillary changes in human brain. An immunocytochemical study with a neurofilament antiserum. J Neuropathol Exp Neurol 42: 69–79

    Article  PubMed  CAS  Google Scholar 

  22. Geisler N, Kaufmann E, Fischer S, Plessmann U, Weber K (1983) Neurofilament architecture combines structural principles of intermediate filaments with carboxyterminal extensions increasing in size between triplet proteins. EMBO J 2: 1295–1302

    PubMed  CAS  Google Scholar 

  23. Gibson PH, Tomlinson BE (1977) Numbers of Hirano bodies in the hippocampus of normal and demented people with Alzheimer’s disease. J Neurol Sci 33: 199–206

    Article  PubMed  CAS  Google Scholar 

  24. Glenner GG, Wong CW (1984) Alzheimer’s disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun 120: 885–890

    Article  PubMed  CAS  Google Scholar 

  25. Goldman JE (1983) The association of actin with Hirano bodies. J Neuropathol Exp Neurol 42: 146–152

    Article  PubMed  CAS  Google Scholar 

  26. 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: 1496–1499

    Article  PubMed  CAS  Google Scholar 

  27. Hedreen JC, Struble RG, Whitehouse PJ, Price DL (1984) Topography of the magnocellular basal forebrain system in human brain. J Neuropathol Exp Neurol 43: 1–21

    Article  PubMed  CAS  Google Scholar 

  28. Hirano A, Zimmerman HM (1962) Alzheimer’s neurofibrillary changes. A topographic study. Arch Neurol 7: 227–242

    PubMed  CAS  Google Scholar 

  29. Hirano A, Dembitzer HM, Kurland LT, Zimmerman HM (1968) The fine structure of some intraganglionic alterations. Neurofibrillary tangles, granulovacuolar bodies and “rod-like” structures as seen in amyotrophic lateral sclerosis and parkinsonism-dementia complex. J Neuropathol Exp Neurol 27: 167–182

    Article  PubMed  CAS  Google Scholar 

  30. Hyman BT, Van Hoesen GW, Damasio AR, Barnes CL (1984) Alzheimer’s disease: cell-specific pathology isolates the hippocampal formation. Science 225: 1168–1170

    Article  PubMed  CAS  Google Scholar 

  31. Jamada M, Mehraein P (1968) Verteilungsmuster der senilen Veränderungen im Gehirn. Die Beteiligung des limbischen Systems bei hirnatrophischen Prozessen des Seniums und bei Morbus Alzheimer. Arch Psychiatr Z Neurol 211: 308–324

    Article  CAS  Google Scholar 

  32. Kemper TL (1983) Organization of the neuropathology of the amygdala in Alzheimer’s disease. Biological aspects of Alzheimer’s Disease. Banbury Rep 15: 31–35

    Google Scholar 

  33. Kidd M (1963) Paired helical filaments in electron microscopy of Alzheimer’s disease. Nature 197: 192–193

    Article  PubMed  CAS  Google Scholar 

  34. Kitt CA, Price DL, Struble RG, Cork LC, Wainer BH, Becher MW, Mobley WC (1984) Evidence for cholinergic neurites in senile plaques. Science 226: 1443–1445

    Article  PubMed  CAS  Google Scholar 

  35. Kitt CA, Struble RG, Cork LC, Mobley WC, Walker LC, Joh TH, Price DL (in press) Catecholaminergic neurites in senile plaques in prefrontal cortex of aged nonhuman primates. Neuroscience 16:691–699

    Google Scholar 

  36. Lewis SA, Cowan NJ (in press) Temporal expression of mouse GFAP mRNA studied by a rapid in situ hybridization procedure. J Neurochem

    Google Scholar 

  37. Mash DC, Flynn DD, Potter LT (1985) Loss of M2 muscarine receptors in the cerebral cortex in Alzheimer’s disease and experimental cholinergic denervation. Science 228: 1115–1117

    Article  PubMed  CAS  Google Scholar 

  38. Mesulam MM, Mufson EJ, Levey AI, Wainer BH (1983) Cholinergic innervation of cortex by the basal forebrain: cytochemistry and cortical connections of the septal area, diagonal band nuclei, nucleus basalis (substantia innominata), and hypothalamus in the rhesus monkey. J Comp Neurol 214: 170–197

    Article  PubMed  CAS  Google Scholar 

  39. Morrison JH, Rogers J, Scherr S, Benoit R, Bloom FE (1985) Somatostatin immunoreactivity in neuritic plaques of Alzheimer’s patients. Nature 314: 90–94

    Article  PubMed  CAS  Google Scholar 

  40. Mountjoy CQ, Roth M, Evans NJR, Evans HM (1983) Cortical neuronal counts in normal elderly controls and demented patients. Neurobiol Aging 4: 1–11

    Article  PubMed  CAS  Google Scholar 

  41. Nukina N, Ihara Y (1983) Immunocytochemical study on senile plaques in Alzheimer’s disease. II. Abnormal dendrites in senile plaques as revealed by antimicrotubule-associated proteins (MAPs) immunostaining. Proc Jpn Acad 59: 288–292

    Article  CAS  Google Scholar 

  42. Perl DP, Brody AR (1980) Alzheimer’s disease: X-ray spectrometric evidence of aluminum accumulation in neurofibrillary tangle-bearing neurons. Science 208: 297–299

    Article  PubMed  CAS  Google Scholar 

  43. Perry EK, Perry RH (1985) New insights into the nature of senile (Alzheimer-type) plaques. Trends Neurosci 8: 301–303

    Article  Google Scholar 

  44. Perry EK, Perry RH, Candy JM, Fairbairn AF, Blessed G, Dick DJ, Tomlinson BE (1984) Cortical serotonin-S2 receptor binding abnormalities in patients with Alzheimer’s disease: comparisons with Parkinson’s disease. Neurosci Lett 51: 353–357

    Article  PubMed  CAS  Google Scholar 

  45. Perry EK, Tomlinson BE, Blessed G, Bergmann K, Gibson PH, Perry RH (1978) Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. Br Med J 2: 1457–1459

    Article  PubMed  CAS  Google Scholar 

  46. Perry RH, Candy JM, Perry EK (1983) Some observations and speculations concerning the cholinergic system and neuropeptides in Alzheimer’s disease. Biological aspects of Alzheimer’s Disease. Banbury Rep 15: 351–361

    Google Scholar 

  47. Powers JM, Schlaepfer WW, Willingham MC, Hall BJ (1981) An immunoperoxidase study of senile cerebral amyloidosis with pathogenetic considerations. J Neuropathol Exp Neurol 40: 592–612

    Article  PubMed  CAS  Google Scholar 

  48. Price DL, Cork LC, Stuble RG, Kitt CA, Price DL Jr, Lehmann J, Hedreen JC (1985) Neuropathological, neurochemical, and behavioral studies of the aging nonhuman primate. In: Davis RT, Leathers CW (eds) Behavior and pathology of aging in Rhesus monkeys. Alan R. Liss, New York

    Google Scholar 

  49. Price DL, Whitehouse PJ, Struble RG, Coyle JT, Clark AW, DeLong MR, Cork LC, Hedreen JC (1982) Alzheimer’s disease and Down’s syndrome. Ann NY Acad Sci 396: 145–164

    Article  PubMed  CAS  Google Scholar 

  50. Price DL, Whitehouse PJ, Struble RG, Price DL Jr, Cork LC, Hedreen JC, Kitt CA (1983) Basal forebrain cholinergic neurons and neuritic plaques in primate brain. Biological Aspects of Alzheimer’s Disease. Banbury Rep 15: 65–77

    Google Scholar 

  51. Probst A, Basler V, Bron B, Ulrich J (1983) Neuritic plaques in senile dementia of Alzheimer type: a Golgi analysis in the hippocampal region. Brain Res 268: 249–254

    Article  PubMed  CAS  Google Scholar 

  52. Probst A, Ulrich J, Heitz PU (1982) Senile dementia of Alzheimer type: astroglial reaction to extracellular neurofibrillary tangles in the hippocampus. Acta Neuropathol (Berl) 57: 75–79

    Article  CAS  Google Scholar 

  53. Roberts GW, Crow TJ, Polak JM (1985) Location of neuronal tangles in somatostatin neurones in Alzheimer’s disease. Nature 314: 92–94

    Article  PubMed  CAS  Google Scholar 

  54. Rossor MN, Emson PC, Mountjoy CQ, Roth M, Iversen LL (1980) Reduced amounts of immunoreactive somatostatin in the temporal cortex in senile dementia of Alzheimer type. Neurosci Lett 20: 373–377

    Article  PubMed  CAS  Google Scholar 

  55. Saper CB, German DC, White CL III (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: 1089–1095

    PubMed  CAS  Google Scholar 

  56. Scheibel AB (1979) Dendritic changes in senile and presenile dementias. In: Katzman R (ed) Congenital and acquired cognitive disorders. Raven, New York, pp 107–124

    Google Scholar 

  57. Sims NR, Bowen DM, Allen SJ, Smith CCT, Neary D, Thomas DJ, Davison AN (1983) Presynaptic cholinergic dysfunction in patients with dementia. J Neurochem 40: 503–509

    Article  PubMed  CAS  Google Scholar 

  58. Struble RG, Cork LC, Whitehouse PJ, Price DL (1982) Cholinergic innervation in neuritic plaques. Science 216: 413–415

    Article  PubMed  CAS  Google Scholar 

  59. Struble RG, Hedreen JC, Cork LC, Price DL (1984) Acetylcholinesterase activity in senile plaques of aged macaques. Neurobiol Aging 5: 191–198

    Article  PubMed  CAS  Google Scholar 

  60. Struble RG, Kitt CA, Walker LC, Cork LC, Price DL (1984) Somatostatinergic neurites in senile plaques of aged non-human primates. Brain Res 324: 394–396

    Article  PubMed  CAS  Google Scholar 

  61. Struble RG, Lehmann J, Mitchell SJ, Cork LC, Coyle JT, Price DL, DeLong MR, Antuono PG (in press) Cortical cholinergic innervation: distribution and source in monkeys. In: Hanin I (ed) Dynamics of cholinergic function. Plenum, New York

    Google Scholar 

  62. Struble RG, Powers RE, Casanova MF, Kitt CA, O’Connor DT, Price DL (1985) Multiple transmitter-specific markers in senile plaques in Alzheimer’s disease. J Neuropathol Exp Neurol 44: 325

    Article  Google Scholar 

  63. Struble RG, Price DL Jr, Cork LC, Price DL (1985) Senile plaques in cortex of aged normal monkeys. Brain Res 361: 267–275

    Article  PubMed  CAS  Google Scholar 

  64. Tomlinson BE, Kitchener D (1972) Granulovacuolar degeneration of hippocampal pyramidal cells. J Pathol 106: 165–185

    Article  PubMed  CAS  Google Scholar 

  65. Tomlinson BE, Blessed G, Roth M (1970) Observations on the brains of demented old people. J Neurol Sci 11: 205–242

    Article  PubMed  CAS  Google Scholar 

  66. Tomlinson BE, Irving D, Blessed G (1981) Cell loss in the locus coeruleus in senile dementia of Alzheimer type. J Neurol Sci 49: 419–428

    Article  PubMed  CAS  Google Scholar 

  67. Troncoso JC, Hoffman PN, Griffin JW, Hess-Kozlow KM, Price DL (1985) Aluminum intoxication: a disorder of neurofilament transport in motor neurons. Brain Res 342: 172–175

    Article  PubMed  CAS  Google Scholar 

  68. Troncoso JC, Price DL, Griffin JW, Parhad IM (1982) Neurofibrillary axonal pathology in aluminum intoxication. Ann Neurol 12: 278–283

    Article  PubMed  CAS  Google Scholar 

  69. Walker LC, Kitt CA, Struble RG, Schmechel DE, Oertel WH, Cork LC, Price DL (1985) Glutamic acid decarboxylase-like immunoreactivity in senile plaques. Neurosci Lett 59: 165–169

    Article  PubMed  CAS  Google Scholar 

  70. Whitehouse PJ, Martino AM, Antuono PG, Coyle JT, Price DL, Kellar KJ (1985) Reductions in nicotinic receptors measured using [3H] acetylcholine in Alzheimer’s disease. Soc Neurosci Abstr 11: 134

    Google Scholar 

  71. Whitehouse PJ, Price DL, Struble RG, Clark AW, Coyle JT, DeLong MR (1982) Alzheimer’s disease and senile dementia: loss of neurons in the basal forebrain. Science 215: 1237–1239

    Article  PubMed  CAS  Google Scholar 

  72. Wilcock GK, Esiri MM (1982) Plaques, tangles and dementia. A quantitative study. J Neurol Sci 56: 343–356

    Article  PubMed  CAS  Google Scholar 

  73. Wilcock GK, Esiri MM, Bowen DM, Smith CCT(1982) Alzheimer’s disease. Correlation of cortical choline acetyltransferase activity with the severity of dementia and histological abnormalities. J Neurol Sci 57: 407–417

    Google Scholar 

  74. Winblad B, Adolfsson R, Carlsson A, Gottfries C-G (1982) Biogenic amines in brains of patients with Alzheimer’s disease. In: Corkin S, Davis KL, Growdon JH, Usdin E, Wurtman RJ (eds) Alzheimer’s disease: a report of progress in research. Raven, New York, pp 25–33 (Aging, vol 19 )

    Google Scholar 

  75. Wisniewski HM, Terry RD (1973) Reexamination of the pathogenesis of the senile plaque. In: Zimmerman HM (ed) Progress in neuropathology, vol 2. Grune and Stratton, New York, pp 1–26

    Google Scholar 

  76. Wisniewski HM, Sturman JA, Shek JW (1980) Aluminum chloride induced neurofibrillary changes in the developing rabbit: a chronic animal model. Ann Neurol 8: 479–490

    Article  PubMed  CAS  Google Scholar 

  77. Yamamoto T, Hirano A (1985) Nucleus raphe dorsalis in Alzheimer’s disease: neurofibrillary tangles and loss of large neurons. Ann Neurol 17: 573–577

    Article  PubMed  CAS  Google Scholar 

  78. Yates CM, Simpson J, Gordon A, Maloney AFJ, Allison Y, Ritchie IM, Urquhart A (1983) Catecholamines and cholinergic enzymes in pre-senile and senile Alzheimer-type dementia and Down’s syndrome. Brain Res 280: 119–126

    Article  PubMed  CAS  Google Scholar 

  79. DeSouza EB, Whitehouse PJ, Kuhar, MJ, Price DL, Vale WW (1986) Reciprocal changes in corticotropin-releasing factor (CRF)-like immunoreactivity and CRF receptors in cerebral cortex of Alzheimer’s disease. Nature 319: 593–595

    Article  CAS  Google Scholar 

  80. Powers RE, Struble RG, Casanova MF, O’Connor DT, Kitt CA, Price DL (in press) Hippocampal anatomy and structural abnormalities of noradrenergic systems in aging and in Alzheimer’s disease. Neuroscience

    Google Scholar 

  81. Price DL, Altschuler RJ, Struble RG, Casanova MF, Cork LC, Murphy DB (in press) Sequestration of tubulin in neurons in Alzheimer’s disease. Brain Res

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Neuropathology Laboratory, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    J. C. Troncoso

Authors
  1. D. L. Price
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. G. Struble
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L. C. Cork
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P. J. Whitehouse
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. C. A. Kitt
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J. C. Troncoso
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Abteilung Neurologie, R.W.T.H., Pauwelsstraße, 5100, Aachen, Germany

    Klaus Poeck

  2. Neurologische Universitätsklinik, Moorenstraße 5, 4000, Düsseldorf, Germany

    Hans-Joachim Freund

  3. Neurologische Universitätsklinik, Voßstraße 2, 6900, Heidelberg, Germany

    Heinz Gänshirt

Rights and permissions

Reprints and permissions

Copyright information

© 1986 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Price, D.L., Struble, R.G., Cork, L.C., Whitehouse, P.J., Kitt, C.A., Troncoso, J.C. (1986). Classical and Modern Neuropathological Approaches to Alzheimer’s Disease. In: Poeck, K., Freund, HJ., Gänshirt, H. (eds) Neurology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-70007-1_11

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-70007-1_11

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-70009-5

  • Online ISBN: 978-3-642-70007-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation