The neuropathological diagnosis of Alzheimer disease

  • K. A. Jellinger
Part of the Journal of Neural Transmission. Supplementa book series (NEURAL SUPPL, volume 53)


The unequivocal diagnosis of Alzheimer disease (AD) rests on histopathological evidence at brain autopsy or biopsy. Although the histological features of AD are well known, defining criteria for the morphological diagnosis of AD is difficult due to the phenotypical heterogeneity of the disease, absence of specific markers, and overlap of AD pathology with that observed in non-demented elderly individuals. This gray zone between normal to pathological aging and full-fledged AD represents an important diagnostic problem and should be overcome by better standardized criteria that will allow to minimize interrater and interlaboratory variability in the diagnosis of AD. Current criteria for the neuropathological diagnosis of AD are based on age-related (semi)quantitative assessment of “senile” plaques (NIA criteria), neuritic plaques (CERAD), plaques and neurofibrillary tangles in neocortex and hippocampus (Tierney et al., 1988), and staging of hierarchic spreading of neuritic AD changes, in particular, neurofibrillary tangles (Braak and Braak, 1991). All these algorithms have some weaknesses and do not recognize the various subtypes of AD. Multivariant analysis of an autopsy series of elderly subjects revealed significant correlations between psychostatus assessed by the Mini-Mental State and both the CERAD criteria and Braak staging. Although the role of plaques and tangles in the pathogenesis of AD and their relationship to both neuronal loss and dementia remain to be elucidated, clinicopathological studies have shown that both lesions, if present in sufficient numbers, particularly in the neocortex, are considered the best correlates for AD related dementia. Recent consensus recommendations of the NIA-and Reagan Institute Working Group for the morphological diagnosis of AD consider AD as a heterogenous clinicopathological entity. After exclusion of other causes of dementia, the likelihood that AD accounts for dementia is considered high, intermediate or low according to the frequency of neuritic AD lesions with regard to both the CERAD criteria and Braak staging. The evaluation of small autopsy series according to these criteria demonstrated their easy and rapid application in AD and non-demented subjects, with much less reliability for other dementing disorders.


Alzheimer Disease Dementia With Lewy Body Progressive Supranuclear Palsy Neurofibrillary Tangle Neuritic Plaque 
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  1. Arriagada PV, Growdon JH, Hedley-Whyte T, Hyman BT (1992) Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer’s disease. Neurology 42: 631–639PubMedCrossRefGoogle Scholar
  2. Bancher C, Jellinger K, Lassmann H, Fischer P, Leblhuber F (1996) Correlations between mental state and quantitative neuropathology in the Vienna Prospective Longitudinal Study on Dementia. Eur Arch Psychiatry Clin Neurosci 246: 137–146PubMedCrossRefGoogle Scholar
  3. Bancher C, Egensperger R, Kösel S, Jellinger K, Graeber MB (1997a) Low prevalence of apolipoprotein E ɛ4 allele in the neurofibrillary tangle predominant form of senile dementia. Acta Neuropathol 94: 403–409PubMedCrossRefGoogle Scholar
  4. Bancher C, Lassmann H, Breitschopf H, Jellinger K (1997) Mechanisms of cell death in Alzheimer’s disease. J Neural Transm [Suppl] 50: 141–152CrossRefGoogle Scholar
  5. Bancher C, Paulus W, Paukner K, Jellinger K (1997c) Neuropathological diagnosis of Alzheimer’s disease: consensus between practicing neuropathologists? Alz Dis Assoc Disord 11: 207–219Google Scholar
  6. Beach TG, Honer WG, Hughes LH (1997) Cholinergic fibre loss associated with diffuse plaques in the non-demented elderly: the preclinical stage of Alzheimer’s disease? Acta Neuropathol 93: 146–151PubMedCrossRefGoogle Scholar
  7. Bennett DA, Cochran EJH, Saper CB (1993) Pathological changes in frontal cortex from biopsy to autopsy in Alzheimer’s disease. Neurobiol Aging 14: 589–596PubMedCrossRefGoogle Scholar
  8. Berg L, McKeel DW, Miller JP, Barty J, Morris JC (1993) Neuropathological indexes of Alzheimer’s disease in demented and nondemented persons aged 80 years and older. Arch Neurol 50: 349–358PubMedCrossRefGoogle Scholar
  9. Bierer LM, Haroutunian V, Gabriel S, Knott PJ, Carlin LS, Purohit DP, Perl DP, Schmeidler J, Kanof P, Davis KL (1995a) Neurochemical correlates of dementia severity in Alzheimer’s disease: relative importance of the cholinergic deficits. J Neurochem 64: 749–760PubMedCrossRefGoogle Scholar
  10. Bierer LM, Hof PR, Purohit DP, Carlin L, Schmeidler J, Davis KL, Perl DP (1995b) Neocortical neurofibrillary tangles correlate with dementia severity in Alzheimer’s disease. Arch Neurol 52: 81–88PubMedCrossRefGoogle Scholar
  11. Blacker D, Albert MS, Bassett SS, Go RC, Harrell LE, Folstein MF (1994) Reliability and validity of NINCDS-ADRDA criteria for Alzheimer’s disease. The National Institute of Mental Health Genetics Initiative. Arch Neurol 51: 1198–1204PubMedCrossRefGoogle Scholar
  12. Blennow K, Bogdanovic N, Alafuzoff I, Ekman R, Davidson P (1996) Synaptic pathology in Alzheimer’s disease: relation to severity of dementia but not to senile plaques neurofibrillary tangles or the Apo E 4 allele. J Neural Transm 103: 603–618PubMedCrossRefGoogle Scholar
  13. Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82: 239–259PubMedCrossRefGoogle Scholar
  14. Braak H, Braak E (1994) Pathology of Alzheimer’s disease. In: Calne DB (ed) Neurodegenerative diseases. Saunders, Philadelphia, pp 585–613Google Scholar
  15. Braak H, Braak E (1996) Development of Alzheimer-related neurofibrillary changes in the neocortex inversely recapitulates cortical myelogenesis. Acta Neuropathol 92: 197–201PubMedCrossRefGoogle Scholar
  16. Braak H, Duyckaerts C, Braak E, Piette F (1993) Neuropathological staging of Alzheimer-related changes correlates with psychometrically assessed intellectual status. In: Corain B et al (eds) Alzheimer’s disease advances in clinical and basic research. Wiley, Chichester, pp 131–137Google Scholar
  17. Brown J, Lantos PL, Roques P, et al (1996) Familial dementia with swollen achromatic neurons and corticobasal inclusion bodies: a clinical and pathologic study. J Neurol Sci 135: 21–30PubMedCrossRefGoogle Scholar
  18. Callahan LM, Coleman PD (1995) Neurons bearing neurofibrillary tangles are responsible for selected synaptic deficits in Alzheimer’s disease. Neurobiol Aging 16: 311–314PubMedCrossRefGoogle Scholar
  19. Chui HC, Tierney M, Zarow C, Lewis A, Sobel E, Perlmutter LS (1993) Neuropathologic diagnosis of Alzheimer disease: interrater reliability in the assessment of senile plaques and neurofibrillary tangles. Alz Dis Assoc Disord 7: 48–54CrossRefGoogle Scholar
  20. Chui H, Zhang Q, Victoroff J, Zaias B (1996) Differentiating Alzheimer disease and vascular dementia: reframing the question. In: Becker P, Giacobini F (eds) Alzheimer’s disease: from molecular biology to therapy. Birkhäuser, Boston, pp 13–17Google Scholar
  21. Corey-Bloom J, Sabbagh MN, Hansen LA, et al (1997) “Plaque-only” Alzheimer’s disease: a clinical and pathologic examination. Neurology 48: A103CrossRefGoogle Scholar
  22. Crystal HA, Dickson DW, Slowinski MJ, Lipton RB, Grober E, Marks-Nelson H, Antis P (1993) Pathological markers associated with normal aging and dementia in the elderly. Ann Neurol 34: 566–573PubMedCrossRefGoogle Scholar
  23. Cummings PJ, Pike CJ, Shankle R, Cotman CW (1996) Beta-amyloid deposition and other measures of neuropathology predict cogntive status in Alzheimer’s disease. Neurobiol Aging 17: 921–933PubMedCrossRefGoogle Scholar
  24. DeKosky ST, Scheff SW (1990) Synapse loss in frontal cortex biopsies in Alzheimer’s disease: correlation with cognitive severity. Ann Neurol 27: 457–464CrossRefGoogle Scholar
  25. Delaere P, Duyckaerts C, He Y, Piette F, Hauw JJ (1991) Subtypes and differential laminar distribution of βA4 deposits without neuritic plaques or tangles in Alzheimer’s disease: relationship with the intellectual status of 26 cases. Acta Neuropathol 81: 328–338PubMedCrossRefGoogle Scholar
  26. Dickson DW (1997) The pathogenesis of senile plaques. J Neuropathol Exp Neurol 56: 321–339PubMedCrossRefGoogle Scholar
  27. Dickson DW, Crystal HA, Mattiace LA, Masur DM, Blau AD, Davies P, Yen SM, Aronson MN (1991) Identification of normal and pathological aging in prospectively studied nondemented elderly humans. Neurobiol Aging 13: 179–189CrossRefGoogle Scholar
  28. Dickson DW, Crystal HA, Bevona C, Honer W, Vincent I, Davies P (1995) Correlations of synaptic and pathological markers with cognition of the elderly. Neurobiol Aging 16: 285–304PubMedCrossRefGoogle Scholar
  29. Esiri MM, Hyman BT, Beyreuther K, Masters CL (1997) Ageing and dementia. In: Graham DI, Lantos PL (eds) Greenfield’s neuropathology, 6th ed. Arnold, London, pp 152–233Google Scholar
  30. Etiene D, Kraft J, Wands JR, Gomez-Isla T, Hamyn BT, Hedley-White ET, de la Monte SM (1997) Cerebral infarction contributes to the heterogeneity of Alzheimer’s disease (abstr). J Neuropathol Exp Neurol 56: 617CrossRefGoogle Scholar
  31. Folstein MF, Folstein SE, McHugh PR (1975) “Mini-Mental State”: a practical method for grading the cognitive state of patients for the clinician. J Psychiatry Res 12: 189–198CrossRefGoogle Scholar
  32. Foster NL, Wolhelmsen K, Sima AAF, et al (1997) Frontotemporal dementia and parkinsonism linked to chromosome 17: a consensus conference. Ann Neurol 41: 706–715PubMedCrossRefGoogle Scholar
  33. Galasko D, Hansen LA, Katzman R, Widerholt W, Masliah E, Terry RD, Hill LR, Lessin P, Thal LJ (1994) Clinical-neuropathological correlations in Alzheimer’s disease and related dementias. Arch Neurol 51: 888–895PubMedCrossRefGoogle Scholar
  34. Gearing M, Mirra SS (1997) Alzheimer’s disease with concomitant Parkinson’s disease changes: Two subgroups defined by neurofibrillary pathology (abstr). J Neuropathol Exp Neurol 56: 616CrossRefGoogle Scholar
  35. Gearing M, Mirra SS, Hedreen JC, Sumi SM, Hansen LA, Heyman A (1995) The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD), part X. Neuropathology confirmation of the clinical diagnosis of Alzheimer’s disease. Neurology 45: 461–461Google Scholar
  36. Gearing M, Schneider LA, Mori H, Mirra SS (1996) Progression of Alzheimer’s disease pathology from biopsy to autopsy (abstr). J Neuropathol Exp Neurol 62: 64Google Scholar
  37. Geddes JW, Tekirian TL, Soultanian NS, et al (1997) Comparison of neuropathologic criteria for the diagnosis of Alzheimer’s disease. Neurobiol Aging 18[Suppl 1]: S99-S105Google Scholar
  38. Gertz HJ, Xuereb JH, Huppert FA, et al (1996) The relationship between clinical dementia and neuropathological staging (Braak) in a very elderly community sample. Eur Arch Psychiatry Clin Neurosci 246: 152–156CrossRefGoogle Scholar
  39. Gertz HJ, Xuereb J, Huppert F, Brayne C, et al. (1998) Examination of the validity of the hierarchical model of neuropathological staging in normal aging and Alzheimer’s disease. Acta Neuropathol 95: 154–158PubMedCrossRefGoogle Scholar
  40. Giannakopoulos P, Hof PR, Kovari E, Vallet P, Hermann FR, Bouras C (1996) Distinct patterns of neuronal loss and Alzheimer’s disease lesion distribution in elderly individuals older than 90 years. J Neuropathol Exp Neurol 55: 1210–1220PubMedCrossRefGoogle Scholar
  41. Gomez-Igla T, Price T, Hyman BT, Morris DW, Growdon JH, Hyman BT (1996) Profound loss of layer II of entorhinal cortex neurons in very mild Alzheimer’s disease. J Neurosci 16: 4491–4500Google Scholar
  42. Hansen LA, Masliah E, Galasko D, Terry RD (1993) Plaque-only Alzheimer disease is usually the Lewy body variant and vice versa. J Neuropathol Exp Neurol 52: 648–654PubMedCrossRefGoogle Scholar
  43. Heinonen O, Soininen H, Sorvari H, Kosunen O, Paljärvi I, Koivisto E, Riekkienen PJ (1995) Loss of synaptophysin-like immunoreactivity in the hippocampal formation as an early phenomenon in Alzheimer’s disease. Neuroscience 64: 375–384PubMedCrossRefGoogle Scholar
  44. Hof PR, Morrison JH (1994) The cellular basis of cortical disconnection in Alzheimer disease and related dementing conditions. In: Terry RD, Katzman R, Bick KL (eds) Alzheimer disease. Raven Press, New York, pp 197–229Google Scholar
  45. Hsiao K, Chapman P, Nilsen S, et al (1996) Correlative memory deficits, Aβ elevation, and amyloid plaques in transgenic mice. Science 274: 99–102PubMedCrossRefGoogle Scholar
  46. Hyman BT (1996) Anatomy of pathological alterations in Alzheimer’s disease. In: Wlasco W, Tanzi E (eds) Molecular mechanisms of dementia. Humana Press, Totowa, NJ, pp 219–223CrossRefGoogle Scholar
  47. Hyman BT, Trojanowski JQ (1997) Editorial on Consensus recommendations for the postmortem diagnosis of Alzheimer disease from the National Institute on Aging and the Reagan Institute Working group on diagnostic criteria for the neuropathological assessment of Alzheimer disease. J Neuropathol Exp Neurol 56: 1095–1097PubMedCrossRefGoogle Scholar
  48. Ikeda K, Akiyama H, Arai T, Sahara N, Mori H, Usami M, Sakata M, Mizutani T, Wakabayashi K, Takahashi H (1997) A subset of senile dementia high incidence of the ApoE e2 allele. Ann Neurol 41: 693–695PubMedCrossRefGoogle Scholar
  49. Jellinger KA (1996) Structural basis of dementia in neurodegenerative disorders Neuropathological overview. J Neural Transm [Suppl] 47: 1–29CrossRefGoogle Scholar
  50. Jellinger KA, Bancher C (1997) Proposals for re-evaluation of current autopsy criteria for the diagnosis of Alzheimer’s disease. Neurobiol Aging 18: S4: S55–S65PubMedCrossRefGoogle Scholar
  51. Kasa P, Rakonczay Z, Gulyai K (1997) The cholinergic system in Alzheimer’s disease. Progr Neurobiol 52: 511–535CrossRefGoogle Scholar
  52. Katzman R, Terry R, DeTeresa R, Brown T, Davies P, Fuld P, Renbig X, Peck A (1988) Clinical pathological and neurochemical changes in dementia: a subgroup with preserved mental status and numerous neocortical plaques. Ann Neurol 23: 138–144PubMedCrossRefGoogle Scholar
  53. Khachaturian ZS (1985) Diagnosis of Alzheimer’s disease. Arch Neurol 42: 1097–1105PubMedCrossRefGoogle Scholar
  54. Klatka LA, Schiffer RB, Powers JM, Kazee AM (1996) Incorrect diagnosis of Alzheimer’s disease A clinicopathological study. Arch Neurol 53: 35–42PubMedCrossRefGoogle Scholar
  55. Kosunen O, Soininen H, Paljarvi L, Heinonen O, Talasniemi S, Riekkinen S (1996) Diagnostic accuracy of Alzheimer’s disease: a neuropathologic study. Acta Neuropathol 91: 185–193PubMedCrossRefGoogle Scholar
  56. Lassmann H, Weiler R, Fischer P, Bancher C, Jellinger K (1992) Synaptic pathology in Alzheimer’s disease: immunological data for markers of synaptic and large dense core vesicles. Neuroscience 46: 1–8PubMedCrossRefGoogle Scholar
  57. Lassmann H, Bancher C, Breitschopf H, Wegiel F, Bobinski M, Jellinger K, Wisniewski HM (1995) Cell death in Alzheimer’s disease evaluated by DNA fragmentation in situ. Acta Neuropathol 89: 35–41PubMedCrossRefGoogle Scholar
  58. Litvan I, Hauw JJ, Bartko JJ, et al (1996) Validity and reliability of the preliminary NINDS neuropathological criteria for progressive supranuclear palsy and related disorders. J Neuropathol Exp Neurol 55: 97–105PubMedCrossRefGoogle Scholar
  59. Mackenzie IRA (1994) Senile plaques do not progressively accumulate with normal aging. Acta Neuropathol 87: 520–525PubMedCrossRefGoogle Scholar
  60. Mackenzie IRA, McLachlan RS, Kubu CS, Miller LA (1996) Prospective neuro-psychological assessment of nondemented patients with biopsy proven senile plaques. Neurology 46: 425–429PubMedCrossRefGoogle Scholar
  61. Masliah E, Mallory M, Alford M, Ge N, Mucke L (1995) Abnormal synaptic regeneration in hAPP695 transgenic and APOE knockout mice. In: Iqbal K, Mortimer JA, Winblad B, Wisniewski HM (eds) Research advances in Alzheimer’s disease and related disorders. Wiley, London, pp 405–414Google Scholar
  62. McKee AC, Kosik KS, Kowall NW (1992) Neuritic pathology and dementia in Alzheimer’s disease. Ann Neurol 30: 156–165CrossRefGoogle Scholar
  63. McKeel DW Jr, Ball MJ, Price JL, Smith DS, Miller JP, Berg L (1993) Interlaboratory histopathologic assessment of Alzheimer’s neuropathology: different methodologies yield comparable diagnostic results. Alz Dis Assoc Disord 7: 136–153CrossRefGoogle Scholar
  64. McKeith IG, Galasko D, Kosaka K, Perry EK, Dickson DW, Hansen LA, Salmon DP, Lowe J, Mirra SS, Byrne EJ, Quinn NP, Edwardson JA, Ince PG, Bergeron C, Burns A, Miller BL, Loverstone S, Collerton D, Jansen ENH, de Vos RAI, Wilcock GK, Jellinger KA, Perry RH (1996) Clinical and pathological diagnosis of dementia with Lewy bodies (DLB): report of the CDLB International Workshop. Neurology 47: 1113–1124PubMedCrossRefGoogle Scholar
  65. Mirra SS, Heyman A McKeel D, Sumi SM, Crain BJ, Brownlee LM, Vogel FS, Hughes JP, Van Belle G, Berg L (1991) The Consortium to establish a registry for Alzheimer’s disease (CERAD) II. Standardization of the neuropathologic assessment of Alzheimer’s disease. Neurology 41: 479–486PubMedCrossRefGoogle Scholar
  66. Mirra SS, Hart MN, Terry RD (1993) Making the diagnosis of Alzheimer’s disease. Arch Pathol Lab Med 117: 132–144PubMedGoogle Scholar
  67. Mirra SS, Gearing M, McKeel D, Crain BJ, Hughes JP, Van Belle G, Heyman A (1994) Interlaboratory comparison of neuropathology assessments in Alzheimer’s disease: a study of the Consortium to Establish a Registry for Alzheimer’s disease (CERAD). J Neuropathol Exp Neurol 53: 303–315PubMedCrossRefGoogle Scholar
  68. Mirra SS, Gearing M, Nash F (1997) Neuropathologica assessment of Alzheimer’s disease. Neurology 49[Suppl 3]: S14–S16PubMedCrossRefGoogle Scholar
  69. Morris JC, Storandt M, McKeel DW, Rubin EH, Price JL, Grant EA, Berg L (1996) Cerebral amyloid deposition and diffuse plaques in “normal” aging: Evidence for presymptomatic and very mild Alzheimer’s disease. Neurology 46: 707–719PubMedCrossRefGoogle Scholar
  70. Nagy Z, Esiri MM, Jobst KA, et al (1995) Relative roles of plaques and tangles in the dementia of Alzheimer’s disease: correlations using three sets of neuropathological criteria. Dementia 6: 21–31PubMedGoogle Scholar
  71. Nagy Z, Jobst KA, Esiri MM, et al (1996) Hippocampal pathology reflects memory deficit and brain imaging measurements in Alzheimer’s disease: Clinicopathologic correlations using three sets of pathologic diagnostic criteria. Dementia 7: 76–81PubMedGoogle Scholar
  72. Nagy Z, Esiri MM, Cate AM, Smith AD (1997a) Cell cycle markers in the hippocampus in Alzheimer’s disease. Acta Neuropathol 94: 6–15PubMedCrossRefGoogle Scholar
  73. Nagy Z, Esiri MM, Jobst KA, et al (1997b) The effects of additional pathology on the cognitive deficit in Alzheimer disease. J Neuropathol Exp Neurol 56: 165–170PubMedCrossRefGoogle Scholar
  74. Nagy Z, Vatter-Büttner B, Braak H, et al (1997c) Staging of Alzheimer-type pathology: an interrater-intrarater study. Dementia 8: 248–251Google Scholar
  75. Newell K, Hyman B, Growdon J, Hedley-Whyte ET (1997) Evaluation of NIA-Reagan institute criteria for the neuropathological diagnosis of Alzheimer’s disease (abstr). J Neuropathol Exp Neurol 56: 593CrossRefGoogle Scholar
  76. Paulus W, Bancher C, Jellinger K (1992) Interrater reliability in the neuropathologic diagnosis of Alzheimer’s disease. Neurology 42: 329–332PubMedCrossRefGoogle Scholar
  77. Perl DP, Purohit DP, Haroutunian V (1997) Clinicopathologic correlations of the Alzheimer’s disease staging system introduced by Braak and Braak (abstr). J Neuropathol Exp Neurol 56: 577CrossRefGoogle Scholar
  78. Perry EK, Court JA, Lloyd S, Johnson M, Griffiths MH, Spurden D, Piggott MA, Turner J, Perry RH (1996) β-amyloidosis in normal aging and transmitter signaling in human temporal lobe. Ann NY Acad Sci 777: 388–392PubMedCrossRefGoogle Scholar
  79. Poirier J, Aubert I, Quirion R, et al (1996) Apolipoprotein E4 and cholinergic activity in Alzheimer’s brains. In: Becker R, Giacobini E (eds) Alzheimer disease: from molecular biology to therapy. Birkhäuser, Boston, pp 55–60Google Scholar
  80. Pratt S, Prinz M, Mitrovic T, Cervos-Navarro J (1995) Neuropathological diagnostic criteria for vascular dementia. In: Cruz-Sanchez FF, Ravid R, Cuzner M (eds) Neuropathological diagnostic criteria for brain banking. IOS Press, Amsterdam, pp 55–64Google Scholar
  81. Price JL, Davis PB, Morris JC, White DL (1992) The distribution of tangles, plaques and related immunohistochemical markers in healthy aging and Alzheimer’s disease. Neurobiol Aging 12: 295–312CrossRefGoogle Scholar
  82. Rasmussen DX, Brandt J, Stelle C, et al (1996) Accuracy of clinical diagnosis of Alzheimer disease and clinical features of patients with non-Alzheimer disease neuropathology. Alzheimer Dis Assoc Disord 10: 180–188CrossRefGoogle Scholar
  83. Reed LA, Grabowski TJ, Schmidt ML, et al (1997) Autosomal dominant dementia with widespread neurofibrillary tangles. Ann Neurol 42: 564–572PubMedCrossRefGoogle Scholar
  84. Samuel W, Masliah E, Hill R, Butters N, Terry R (1994) Hippocampal connectivity and Alzheimer’s dementia: effects of synapse loss and tangle frequency in a two-component model. Neurology 44: 2081–2088PubMedCrossRefGoogle Scholar
  85. Samuel W, Terry RD, DeTeresa R, Butters N, Masliah E (1994) Clinical correlates of cortical and nucleus basalis pathology in Alzheimer dementia. Arch Neurol 51: 772–778PubMedCrossRefGoogle Scholar
  86. Scheff SW, Price DA (1993) Synapse loss in the temporal lobe in Alzheimer’s disease. Ann Neurol 33: 190–199PubMedCrossRefGoogle Scholar
  87. Sima AAF, Defendini R, Keohane C, et al (1996) The neuropathology of chromosome 17-linked dementia. Ann Neurol 39: 734–743PubMedCrossRefGoogle Scholar
  88. Snowdon DA, Greiner LH, Mortimer JA, Riley KP, Greiner PA, Markesbery MR (1997) Brain infarction and the clinical expression of Alzheimer’s disease. The Nun study. JAMA 277: 813–817CrossRefGoogle Scholar
  89. Spillantini MG, Crowther RA, Goedert M (1996) Comparison of the neurofibrillary pathology in Alzheimer’s disease and familial presenile dementia with tangles. Acta Neuropathol 92: 42–48PubMedCrossRefGoogle Scholar
  90. Sumi SM, Bird TD, Nochlin D, Raskind MA (1992) Familial presenile dementia with psychosis associated with cortical neurofibrillary tangles and degeneration of the amygdala. Neurology 42: 120–127PubMedCrossRefGoogle Scholar
  91. Terry RD (1996) Basis of structural Alzheimer disease and some pathogenic concepts. In: Becker P, Giacobini F (eds) Alzheimer’s disease: from molecular biology to therapy. Birkhäuser, Boston, pp 19–23Google Scholar
  92. Terry RD, Masliah E, Salmon DP (1991) Physical basis of cognitive alterations in Alzheimer’s disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol 30: 572–580PubMedCrossRefGoogle Scholar
  93. Tierney MC, Fischer H, Lewis AJ, Zorzitto ML, Snow WG, Reid DW, Nieuwstraten P (1988) The NINCDS-ADRDA Work Group criteria for the clinical diagnosis of probable Alzheimer’s disease: clinicopathological study of 57 cases. Neurology 38: 356–364CrossRefGoogle Scholar
  94. Trojanowski JQ, Shin RW, Schmidt ML, Lee VMY (1995) Relationship between plaques tangles and dystrophic processes in Alzheimers disease. Neurobiol Aging 16: 335–340PubMedCrossRefGoogle Scholar
  95. Troncoso JC, Suknov RR, Kawas CH, Koliatsos VE (1996a) In situ labelling of dying cortical neurons in normal aging and in Alzheimer’s disease: correlations with senile plaques and disease progression. J Neuropathol Exp Neurol 55: 1134–1142PubMedCrossRefGoogle Scholar
  96. Troncoso JC, Margin LJ, Dal Forno G, Kawas CH (1996b) Neuropathology in controls and demented subjects from the Baltimore longitudinal study of aging. Neurobiol Aging 17: 365–371PubMedCrossRefGoogle Scholar
  97. Ulrich J, Spillantini MG, Goedert M, Dukas L, Stähelin HB (1992) Abundant neurofibrillary tangles without senile plaques in a subset of patients with senile dementia. Neurodegeneration 1: 257–284Google Scholar
  98. Vermersch P, David JP, Frigard B, Falletbianco C, Wattez A, Petit H, Delacourte A (1995) Cortical mapping of Alzheimer pathology in brains of aged non-demented subjects. Progr Neuropsychopharmacol Biol Psychiatry 19: 1035–1047CrossRefGoogle Scholar
  99. Vickers JC (1997) A cellular mechanism for the neuronal changes underlaying Alzheimer’s disease. Neuroscience 78: 629–639PubMedCrossRefGoogle Scholar
  100. Wang D, Munoz DG (1995) Qualitative and quantitative differences in senile plaque dystrophic neurites of Alzheimer’s disease and normal aged brain. J Neuropathol Exp Neurol 54: 548–556PubMedCrossRefGoogle Scholar
  101. Wilcock GK, Esiri MM (1982) Plaques tangles and dementia. A quantitative study. J Neurol Sci 56: 343–356PubMedCrossRefGoogle Scholar
  102. Zhan S-S, Veerhuis R, Kamphorst W, Eikelenboom P (1995) Distribution of beta amyloid associated proteins in plaques in Alzheimer’s disease and in the non-demented elderly. Neurodegeneration 4: 291–297PubMedCrossRefGoogle Scholar

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© Springer-Verlag Wien 1998

Authors and Affiliations

  • K. A. Jellinger
    • 1
  1. 1.Ludwig Boltzmann Institute of Clinical NeurobiologyWienAustria

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