Advertisement

Morphology of Alzheimer’s disease and related disorders

  • K. Jellinger
Part of the Key Topics in Brain Research book series (KEYTOPICS)

Summary

The diagnosis of Alzheimer’s disease (AD) can made with certainty only by histological examination of the brain, either on biopsy or at autopsy, using current criteria that are critically discussed. The morphologic diagnosis of AD is based on the finding of more than certain minimum age-related numbers of neuritic plaques (NP) and neurofibrillary tangles (NFT) that may occur independently from each other and show specific, often bilaterally symmetrical distribution patterns. Although both NFT and NP represent useful diagnostic markers and their concentrations in neocortex correlate reasonably well with certain mental status tests and some biochemical data, progressive loss of neurons and synapses in cortex and brainstem appear to be more correlated with both dementia and neuromediator changes, but their causal relationship with amyloid deposition and cytoskeletal lesions is not clear. Cortical atrophy with 40 to 60% loss of large neurons and 45 to 55% decline of synaptic density in frontal, temporal, parietal cortex and hippocampus are probable correlates of progressive dementia. Many mediator specific brainstem nuclei show progressive neuronal loss and presence of NFT with severe involvement of cholinergic nucleus basalis of Meynert (15 to 90% cell loss and atrophy of large neurons), pedunculopontine and Westphal-Edinger nuclei, serotonergic dorsal raphe nucleus (10 to 76% cell loss), noradrenergic locus ceruleus (40 to 80% cell loss in topographic relation to temporal targets) and, less, the dopaminergic striatonigral system. The morphologic heterogeneity of AD shows overlaps with Parkinson’s, diffuse Lewy body disease, cerebrovascular and other brain lesions. In autopsy series, the accuracy rates for clinical diagnosis of AD are about 80 to 85%, but more standardized morphologic criteria are needed.

Keywords

Alzheimer Disease Cerebral Amyloid Angiopathy Neuritic Plaque Diffuse Lewy Body Disease Mental Status Test 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Adams I (1987) Comparison of synaptic changes in the precentral and postcentral cerebral cortex of aging humans: a quantitative ultrastructural study. Neurobiol Aging 8: 203–212PubMedCrossRefGoogle Scholar
  2. Allen SJ, Dawbarn D, Wilcock GK (1988) Morphometric immunochemical study in the nucleus basalis of Meynert in Alzheimer’s disease. Brain Res 454: 275 – 281PubMedCrossRefGoogle Scholar
  3. Ball MJ (1989) Neuropathology in the diagnosis of Alzheimer’s disease. In: Hovaguimian T, Henderson S, Khachaturian Z, Orley J (eds) Classification and diagnosis of Alzheimer’s disease. An international perspective. Hogrefe and Huber, Toronto, pp 135–143Google Scholar
  4. Bancher C, Lassmann H, Budka H, Jellinger K, et al (1989) An antigenic profile of Lewy bodies: immunocytochemical indication for protein phosphorylation and ubiquitination. J Neuropathol Exp Neurol 48: 81–93PubMedCrossRefGoogle Scholar
  5. Boller F, Lopez OL, Moossy J (1989) Diagnosis of dementia: clinicopathologic correlations. Neurology 39: 76–79PubMedCrossRefGoogle Scholar
  6. Braak H (1989) Morphology of the cerebral cortex in relation to Alzheimer’s dementia. J Neural Transm (P-DSect) 1: 12CrossRefGoogle Scholar
  7. Braak H, Braak E, Bohl J, Lang W (1989) Alzheimer’s disease: amyloid plaques in the cerebellum. J Neurol Sci 93: 277–287PubMedCrossRefGoogle Scholar
  8. Burke WJ, Chung HD, Huang JS, et al (1988) Evidence for retrograde degeneration of epinephrine neurons in Alzheimer’s disease. Ann Neurol 24: 532–536PubMedCrossRefGoogle Scholar
  9. Burkhardt CR, Filley CM, Kleinschmidt-DeMasters BK, et al (1988) Diffuse Lewy body disease and progressive dementia. Neurology 38: 1520–1528PubMedCrossRefGoogle Scholar
  10. Chan-Palay V, Asan E (1989) Alterations in catecholamine neurons of the locus ceruleus in senile dementia of the Alzheimer type and in Parkinson’s disease. J Comp Neurol 287: 373–392PubMedCrossRefGoogle Scholar
  11. Coleman PD, Flood DG (1987) Neuron numbers and dendritic extent in normal aging and Alzheimer’s disease. Neurobiol Aging 8: 521–545PubMedCrossRefGoogle Scholar
  12. Crystal H, Dickson D, Fuld P, et al (1988) Clinico-pathologic studies in dementia: nondemented subjects with pathologically confirmed Alzheimer’s disease. Neurology 38: 1682–1687PubMedCrossRefGoogle Scholar
  13. Davies L, Wolska B, Hilbich C, et al (1988) A 4 amyloid protein deposition and the diagnosis of Alzheimer’s disease. Neurology 38: 1688–1693PubMedCrossRefGoogle Scholar
  14. Delaere P, Duyckaerts C, Brion JP, et al (1989) Tau, paired helical filaments and amyloid in the neocortex: a morphometric study of 15 cases with graded intellectual status in aging and senile dementia of Alzheimer type. Acta Neuropathol (Berl) 77: 645–653CrossRefGoogle Scholar
  15. Dickson DW, Crystal H, Mattiace L, et al (1989) Diffuse Lewy body disease: light and electron microscopic immunocytochemistry of senile plaques. Acta Neuropathol (Berl) 78: 572–584CrossRefGoogle Scholar
  16. Ferreiro JA, Merskey H, Hachinski VC, et al (1989) Quantitative study A4 immunoreactive senile plaques and microvascular amyloid in Alzheimer’s disease. J Neuropathol Exp Neurol 48: 377CrossRefGoogle Scholar
  17. German DC, White CL III, Sparkman DR (1987) Alzheimer’s disease: neurofibrillary tangles in nuclei that project to the cerebral cortex. Neuroscience 21: 305 – 312PubMedCrossRefGoogle Scholar
  18. Gibb WRG (1989) The neuropathology of parkinsonian disorders. In: Jankovic J, Tolosa E (eds) Parkinson’s disease and movement disorders. Urban and Schwarzenberg, Baltimore Munich, pp 205–223Google Scholar
  19. Gibb WRG, Lees A J (1988) The relevance of the Lewy body in the pathogenesis of idiopathic Parkinson’s disease. J Neurol Neurosurg Psychiatry 51: 745–752PubMedCrossRefGoogle Scholar
  20. Hamos JE, De Gennaro LJ, Drachman DA (1989) Synaptic loss in Alzheimer’s disease and other dementias. Neurology 39: 355–361PubMedCrossRefGoogle Scholar
  21. Hansen LA, DeTeresa R, Davies P, Terry RD (1988) Neocortical morphometry, lesion counts, and choline acetyltransferase levels in the age spectrums of Alzheimer’s disease. Neurology 38: 48–57PubMedCrossRefGoogle Scholar
  22. Hansen LA, Masliah E, Terry RD, Mirra SS (1989) A neuropathological subset of Alzheimer’s disease with concomitant Lewy body disease and spongiform change. Acta Neuropathol (Berl) 78: 194–201CrossRefGoogle Scholar
  23. Hyman BT, Van Hoesen GW, Damasio AR (1987) Alzheimer’s disease: glutamate depletion in the hippocampal perforant pathway zone. Ann Neurol 20: 472–481CrossRefGoogle Scholar
  24. Iseki E, Matsushita M, Kosaka K, et al (1989) Distribution and morphology of brain stem plaques in Alzheimer’s disease. Acta Neuropathol (Berl) 78: 131–136CrossRefGoogle Scholar
  25. Jellinger K (1989) Morphologie des alternden Gehirns and der (prä)senilen Demenzen. In: Platt D, Österreich K (Hrsg) Handbuch der Gerontologie, Bd 5. Fischer, Stuttgart New York, S 3–56Google Scholar
  26. Jellinger K, Danielczyk W, Gabriel E (1989) Clinicopathological analysis of dementia disorders in the aged. J Neuropathol Exp Neurol 48: 379CrossRefGoogle Scholar
  27. Jellinger K, Danielczyk W, Fischer P, Gabriel E (1990) Clinicopathological analysis of dementia disorders in the elderly. J Neurol Sci 95 (in press)Google Scholar
  28. Joachim CL, Morris JH, Selkoe DJ (1988) Clinically diagnosed Alzheimer’s disease: autopsy results in 150 cases. Ann Neurol 24: 50–56PubMedCrossRefGoogle Scholar
  29. Joachim CL, Morris JM, Selkoe DJ (1989) Diffuse senile plaques occur commonly in the cerebellum of Alzheimer’s disease. Am J Pathol 135: 309–320PubMedGoogle Scholar
  30. 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: 198–203PubMedCrossRefGoogle Scholar
  31. Katzman R, Terry R, DeTeresa R, et al (1988) Clinical, pathological, and neuro-chemical changes in dementia: a subgroup with preserved mental status and numerous neocortical plaques. Ann Neurol 23: 138–144PubMedCrossRefGoogle Scholar
  32. Khachaturian ZS (1985) Diagnosis of Alzheimer’s disease. Arch Neurol 42:1097 –1105PubMedCrossRefGoogle Scholar
  33. Kosaka K, Tsuchiya K, Yoshimura M (1988) Lewy body disease with and without dementia. A clinicopathologic study of 35 cases. Clin Neuropathol 7: 299 —305Google Scholar
  34. Lamy C, Duyckaerts C, Delaere P, et al (1989) Comparison of seven staining methods for senile plaques and neurofibrillary tangles in a prospective series of 15 elderly patients. Neuropathol Appl Neurobiol 15: 563–578PubMedCrossRefGoogle Scholar
  35. Lassmann H, Fischer P, Bancher C, Jellinger K (1990) Immunocytochemical and ultrastructural pathology of nerve cells in Alzheimer’s disease and related disorders. In: Maurer K, Riederer P, Beckmann H (eds) Lassmann H, Fischer P, Bancher C, Jellinger K, pp 171–179 ( Key Topics in Bra in Research)Google Scholar
  36. Mann DMA, Marcyniuk B, Yates PI, et al (1988) The progression of the pathological changes of Alzheimer’s disease in frontal and temporal neocortex examined both at biopsy and at autopsy. Neuropathol Appl Neurobiol 14: 177–195PubMedCrossRefGoogle Scholar
  37. Masliah E, Terry RD, DeTeresa R, et al (1989) Morphometric quantification of a synaptic marker in neocortex of Alzheimer and Pick disease. J Neuropathol Exp Neurol 48: 333CrossRefGoogle Scholar
  38. Mirra SS, Brownlee LM, Sumi SM, et al (1989) The CERAD neuropathology protocol: observations on cases clinically diagnosed as probable Alzheimer’s disease. J Neuropathol Exp Neurol 48: 334CrossRefGoogle Scholar
  39. Moossy J, Zubenko GS, Martinez AJ, Rao GR (1988) Bilateral symmetry of morphologic lesions in Alzheimer’s disease. Arch Neurol 45: 251–254PubMedCrossRefGoogle Scholar
  40. Morris JC, McKeel DW, Fulling K, et al (1988) Validation of clinical diagnostic criteria for Alzheimer disease. Ann Neurol 24: 17–22PubMedCrossRefGoogle Scholar
  41. Mufson EJ, Mash DC, Hersh LB (1988) Neurofibrillary tangles in cholinergic pedunculopontine neurons in Alzheimer’s disease. Ann Neurol 24: 623–629PubMedCrossRefGoogle Scholar
  42. Oyanagi K, Takahashi H, Wakabayashi K, Ikuta F (1989) Correlative decrease of large neurons in the neostriatum and basal nucleus of Meynert in Alzheimer disease. J Neuropathol Exp Neurol 48: 336CrossRefGoogle Scholar
  43. Perry RH, Irving D, Blessed G, et al (1990) Senile dementia of Lewy body type. A clinically and neuropathologically distinct form of Lewy body dementia in the elderly. J Neurol Sci 95: 119–139PubMedCrossRefGoogle Scholar
  44. Probst A, Anderton BH, Brion JP, Ulrich JU (1989) Senile plaque neurites fail to demonstrate anti-paired helical filament and anti-microtubule-associated protein-tau immunoreactive proteins in the absence of neurofibrillary tangles in the neocortex. Acta Neuropathol (Berl) 77: 430–436CrossRefGoogle Scholar
  45. Purohit C, Perry RH, Irvinb D (1989) Alzheimer-type pathology in dentate gyrus of the hippocampus. J Neuropathol Exp Neurol 48: 340Google Scholar
  46. Stopa EG, Tate-Ostroff B, Walcott EC (1989) Human suprachiasmatic nuclei in Alzheimer disease. J Neuropathol Exp Neurol 48: 327CrossRefGoogle Scholar
  47. Sulkova R, Erkinjuntti T, Haltia M, et al (1989) Non-Alzheimer dementias fulfilling the NINCDS-ADRDA criteria for probable Alzheimer’s disease. Aging of the brain and dementia: ten years later. Florence, May 31– June 3, 1989, p 125 (Abstr)Google Scholar
  48. Terry RD, Hansen LA, DeTeresa R, et al (1987) Senile dementia of the Alzheimer type without neocortical neurofibrillary tangles. J Neuropathol Exp Neurol 46: 262–268PubMedCrossRefGoogle Scholar
  49. Tierney MC, Fisher RH, Lewis AJ, et al (1988) The NINCDS-ADRDA Work Group criteria for the clinical diagnosis of probable Alzheimer disease: clinicopathologic study of 57 cases. Neurology 38: 359–364PubMedCrossRefGoogle Scholar
  50. Tomlinson BE (1989) The neuropathology of Alzheimer’s disease — Issues in need of resolution. Neuropathol Appl Neurobiol 15: 491–512PubMedCrossRefGoogle Scholar
  51. Tomlinson BE, Henderson G (1976) Some quantitative cerebral findings in normal and demented old people. In: Terry RD, Gershon S (eds) Neurobiology of aging. Raven Press, New York, pp 183–209Google Scholar
  52. Tourtellotte WG, Van Hoesen GW, Hyman BT, et al (1989) Afferents of the thalamic reticular nucleus are pathologically altered in Alzheimer’s disease. J Neuropathol Exp Neurol 48: 336CrossRefGoogle Scholar
  53. Vinters HV, Gray F, Partridge WM, et al (1989) Cerebral amyloid angiopathy with leukoencephalopathy. J Neuropathol Exp Neurol 48: 379CrossRefGoogle Scholar
  54. Vogels OJM, Broere CA J, Renkawek K (1989) Neuron numbers and sizes of nucleus basalis Meynert in Alzheimer’s disease. Aging of the brain and dementia: ten years later. Florence, May 31– June 3, 1989, p 77 (Abstr)Google Scholar
  55. Wegiel J, Wisniewski HM, Wang KC (1989) Neuronal reaction on plaque amyloid deposits. J Neuropathol Exp Neurol 48: 325CrossRefGoogle Scholar
  56. Weis S, Wenger E, Jellinger K (1989) The corpus callosum in normal aging and Alzheimer disease. Aging of the brain and dementia: ten years later. Florence, May 31– June 3, 1989, p 79 (Abstr)Google Scholar
  57. Wisniewski HM, Wen GY, Kim LS (1989) Comparison of four staining methods on the detection of neuritic plaques. Acta Neuropathol (Berl) 78: 22–27CrossRefGoogle Scholar
  58. Yamaguchi H, Hirai S, Morimatsu M, et al (1988) Diffuse type of senile plaques in the cerebellum of Alzheimer type dementia demonstrated by ß-protein immunostaining. Acta Neuropathol 77: 113–114PubMedGoogle Scholar
  59. Zubenko GS, Moossy J, Claassen AJ, et al (1989) Neurochemical and morphological correlates of major depression in primary dementia. J Neuropathol Exp Neurol 48: 333CrossRefGoogle Scholar
  60. Zweig RM, Ross CA, Hedreen JC, et al (1988) The neuropathology of aminergic nuclei in Alzheimer’s disease. Ann Neurol 24: 233–242PubMedCrossRefGoogle Scholar
  61. Zweig RM, Jankel WR, Hedreen JC, et al (1989) The pedunculopontine nucleus in Parkinson’s disease. Ann Neurol 26: 41–46PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 1990

Authors and Affiliations

  • K. Jellinger
    • 1
  1. 1.Ludwig Boltzmann Institute of Clinical NeurobiologyLainz HospitalViennaAustria

Personalised recommendations