Neuropathology of Alzheimer’s disease: a critical update

  • K. A. Jellinger
  • C. Bancher
Part of the Journal of Neural Transmission. Supplementa book series (NEURAL SUPPL, volume 54)


The unequivocal diagnosis of Alzheimer’s disease (AD) rests on histopathological evidence at brain autopsy or biopsy. The morphology of AD includes cerebral atrophy, deposition of βA4 amyloid (Aβ) (senile plaques and amyloid angiopathy), neuritic changes (neuritic plaques, neurofibrillary tangles (NFT) and neuropil threads) with formation of paired helical filaments (PHF) containing polymerized hyperphosphorylated tau protein triplet, causing disruption of the neuronal cytoskeleton with loss of synapses and neurons, with altered cortico-cortical connectivity, leading to disconnection of the cerebral cortex. Defining criteria for the morphologic diagnosis of AD is difficult due to the phenotypic heterogeneity of the disease, the absence of specific markers, and overlap of AD morphology with that observed in non-demented elderly individuals. This gray zone between normal to pathologic 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 morphologic diagnosis of AD are based on (semi)quantitative assessment of diffuse and neuritic plaques (NIA), exclusively neuritic plaques (CERAD), plaques and NFT in neocortex and hippocampus (Tierney et al., 1988), and staging of hierarchic spreading of neuritic AD changes (Braak and Braak, 1991); all of them have weaknesses and need to be revalidated. Multivariant analysis of an autopsy series of elderly subjects revealed significant correlations between psychostatus and both the CERAD criteria and Braak staging. Recent recommendations of the NIA-Reagan Institute for the morphologic diagnosis of AD are presented. Although the role of plaques and NFT in the pathogenesis of AD remains undetermined, clinicopathological correlative studies have shown that both lesions, if present in sufficient numbers, particularly in the neocortex, are considered the best morphological signposts for AD. Recent studies on neuron death in AD that, at least in part, appears different from classical apoptosis and may precede the symptomatic stage of AD, have shown varying results indicating only indirect relationship between DNA fragmentation and both Aβ deposition and NFTs. Both these AD-typical markers appear to increase the risk of cells to degenerate, but are not the sole responsibles of the degenerative process in AD, the basic mechanisms of which remain to be elucidated.


Dementia With Lewy Body Progressive Supranuclear Palsy Senile Plaque Senile Dementia Neuritic Plaque 
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  1. Amagada 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: 631–639Google Scholar
  2. Bancher C, Jellinger K (1994) Neurofibrillary tangle predominant form of senile dementia of Alzheimer type: a rare subtype in very old subjects. Acta Neuropathol 88: 565–570PubMedGoogle Scholar
  3. Bancher C, Braak H, Fischer P, Jellinger K (1993) Neuropathological staging of Alzheimer lesions and intellectual status in Alzheimer’s and Parkinson’s disease. Neurosci Lett 162: 179–182PubMedGoogle Scholar
  4. 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: 137–146PubMedGoogle Scholar
  5. Bancher C, Lassmann H, Breitschopf H, Jellinger K (1997) Mechanisms of cell death in Alzheimer’s disease. J Neural Transm [Suppl] 50: 141–152Google Scholar
  6. Bancher C, Paulus W, Paukner K, Jellinger K (1997a) Neuropathological diagnosis of Alzheimer’s disease: consensus between practicing neuropathologists? Alzheimer Dis Assoc Disord 11: 207–219PubMedGoogle Scholar
  7. Bancher C, Egensperger R, Kösel S, Jellinger K, Graeber MB (1997b) Low prevalence of apolipoprotein E ε4 allele in the neurofibrillary tangle predominant form of senile dementia. Acta Neuropathol 94: 403–409PubMedGoogle Scholar
  8. 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: 146–151PubMedGoogle Scholar
  9. Bennett DA, Cochran EJH, Saper CB (1993) Pathological changes in frontal cortex from biopsy to autopsy in Alzheimer’s disease. Neurobiol Aging 14: 589–596PubMedGoogle Scholar
  10. 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: 349–358PubMedGoogle Scholar
  11. 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: 749–760PubMedGoogle Scholar
  12. 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: 81–88PubMedGoogle Scholar
  13. 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: 1198–1204PubMedGoogle Scholar
  14. 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: 603–618PubMedGoogle Scholar
  15. Bogdanovic N, Morris J (1995) Diagnostic criteria for Alzheimer’s disease in multi-centre brain banking. In: Cruz-Sanchez FF, Ravid R, Cuzner M (eds) Neuropathological diagnostic criteria for brain banking. IOS Press, Amsterdam, pp 20–29Google Scholar
  16. Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82: 239–259PubMedGoogle Scholar
  17. Braak H, Braak E (1996) Development of Alzheimer-related neurofibrillary changes in the neocortex inversely recapitulates cortical myelogenesis. Acta Neuropathol 92: 197–201PubMedGoogle Scholar
  18. 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
  19. Callahan LM, Coleman PD (1995) Neurons bearing neurofibrillary tangles are responsible for selected synaptic deficits in Alzheimer’s disease. Neurobiol Aging 16: 311–314PubMedGoogle Scholar
  20. Chui HC, Tierney M, Zarow C, Lewis A, Sobel E, Perlmutter LS (1993) Neuropathology diagnosis of Alzheimer disease: interrater reliability in the assessment of senile plaques and neurofibrillary tangles. Alzheimer Dis Assoc Disord 7: 48–54PubMedGoogle Scholar
  21. 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
  22. Corey-Bloom J, Sabbagh MN, Hansen LA, et al (1997) “Plaque-only” Alzheimer’s disease: a clinical and pathologic examination. Neurology 48: A103Google Scholar
  23. Crystal H, Dickson D, Fuld P, Masur D, Scott R, Mehler M, Masdeu J, Kawas C, Aronson M, Wolfson L (1988) Clinico-pathological studies in dementia: nondemented subjects with pathologically confirmed Alzheimer’s disease. Neurology 38: 1682–1687PubMedGoogle Scholar
  24. 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: 566–573PubMedGoogle Scholar
  25. DeKosky ST, Scheff SW (1990) Synapse loss in frontal cortex biopsies in Alzheimer’s disease: correlation with cognitive severity. Ann Neurol 27: 457–464PubMedGoogle Scholar
  26. 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: 328–338PubMedGoogle Scholar
  27. Dickson DW (1997) The pathogenesis of senile plaques. J Neuropathol Exp Neurol 56: 321–339PubMedGoogle Scholar
  28. 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: 179–189Google Scholar
  29. Dickson DW, Davies P, Bevona C, et al (1994) Hippocampal sclerosis: a common pathological feature of dementia in very old (80 years of age) humans. Acta Neuropathol 88: 212–221PubMedGoogle Scholar
  30. 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: 285–304PubMedGoogle Scholar
  31. Duyckaerts C, Delaère P, Hauw JJ (1990) Rating of the lesions in senile dementia of the Alzheimer type: concordance between laboratories. J Neurol Sci 97: 295–323PubMedGoogle Scholar
  32. Esiri MM, Hyman BT, Beyreuther K, Masters CL (1997) Ageing and dementia. In: Graham DI, Lantos PL (eds) Greenfield’s neuropathology, 6th ed. E Arnold, London Sidney Auckland, pp 152–233Google Scholar
  33. 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: 189–198Google Scholar
  34. 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: 888–895PubMedGoogle Scholar
  35. 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: 616Google Scholar
  36. 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: 461–461PubMedGoogle Scholar
  37. 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
  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: 152–156Google Scholar
  39. Gertz HJ, Xuereb J, Huppert F, Brayne C, McGee MA, Paykel E, Harrington C, Mukaetova-Ladinska E, Arend T, Wischik CM (1998) Examination of the validity of the hierarchical model of neuropathological staging in normal aging and Alzheimer’s disease. Acta Neuropathol 95: 154–158PubMedGoogle Scholar
  40. Geula C, Mesulam MM, Saroff DM, Wu C-K (1998) Relationship between plaques, tangles, and loss of cortical cholinergic fibers in Alzheimer’s disease. J Neuropathol Exp Neurol 57: 63–75PubMedGoogle Scholar
  41. Giannakopoulos P, Hof PR, Giannakopoulos A-S, Herrmann FR, Michel J-P, Bouras C (1995) Regional distribution of neurofibrillary tangles and senile plaques in the cerebral cortex of very old patients. Arch Neurol 52: 1150–1159PubMedGoogle Scholar
  42. 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: 1210–1220PubMedGoogle Scholar
  43. 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
  44. Gomez-Isla T, Hollister R, West H, et al (1997) Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer’s disease. Ann Neurol 41: 17–24PubMedGoogle Scholar
  45. 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: 648–654PubMedGoogle Scholar
  46. 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: 375–384PubMedGoogle Scholar
  47. Heffernan M, Eastwood JS, Nagy Z, Sanders MW, McDonald B, Harrison PG (1998) Temporal cortex synaptophysin mRNA is reduced in Alzheimer’s disease and is negatively correlated with the severity of dementia. Exp Neurol 150: 235–239PubMedGoogle Scholar
  48. 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
  49. Hsiao K, Chapman P, Nilsen S, et al (1996) Correlative memory deficits, Aβ elevation, and amyloid plaques in transgenic mice. Science 274: 99–102PubMedGoogle Scholar
  50. 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 219–223Google Scholar
  51. 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: 1095–1097PubMedGoogle Scholar
  52. Hyman BT, Marzloff K, Arriagada PV (1993) The lack of accumulation of senile plaques or amyloid burden in Alzheimer’s disease suggests a dynamic balance between amyloid deposition and resolution. J Neuropathol Exp Neurol 52: 594–600PubMedGoogle Scholar
  53. 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 ε2 allele. Ann Neurol 41: 693–695PubMedGoogle Scholar
  54. Jellinger KA (1996) Structural basis of dementia in neurodegenerative disorders Neuropathological overview. J Neural Transm [suppl] 47: 1–29Google Scholar
  55. 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–S65Google Scholar
  56. Jellinger KA, Bancher C (1998) Senile dementia with tangles (tangle predominant form of senile dementia). Brain Pathol 8: 367–376PubMedGoogle Scholar
  57. Jellinger K, Bancher C, Fischer P, Lassmann H (1992) Quantitative histopathologic validation of senile dementia of the Alzheimer type. Eur J Gerontol 3: 146–156Google Scholar
  58. Kasa P, Rakonczay Z, Gulyai K (1997) The cholinergic system in Alzheimer’s disease. Progr Neurobiol 52: 511–535Google Scholar
  59. 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: 138–144PubMedGoogle Scholar
  60. Kazee AM, Eskin TA, Lapham LW, Gabriel RR, McDaniel RD, Hamill RW (1993) Clinicopathologic correlates in Alzheimer’s disease — assessment of clinical and pathologic diagnostic criteria. Alzheimer Dis Assoc Disord 7: 152–164PubMedGoogle Scholar
  61. Khachaturian ZS (1985) Diagnosis of Alzheimer’s disease. Arch Neurol 42: 1097–1105PubMedGoogle Scholar
  62. Klatka LA, Schiffer RB, Powers JM, Kazee AM (1996) Incorrect diagnosis of Alzheimer’s disease A clinicopathological study. Arch Neurol 53: 35–42PubMedGoogle Scholar
  63. 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: 185–193PubMedGoogle Scholar
  64. 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: 1–8PubMedGoogle Scholar
  65. 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: 35–41PubMedGoogle Scholar
  66. Leverenz JB, Raskind MA (1998) Early amyloid deposition in medial temporal lobe of young Down syndrome patients: a regional quantitative analysis. Exp Neurol 150: 296–304PubMedGoogle Scholar
  67. 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: 97–105PubMedGoogle Scholar
  68. Mackenzie IRA (1994) Senile plaques do not progressively accumulate with normal aging. Acta Neuropathol 87: 520–525PubMedGoogle Scholar
  69. Mackenzie IRA, McLachlan RS, Kubu CS, Miller LA (1996) Prospective neuropsychological assessment of nondemented patients with biopsy proven senile plaques. Neurology 46: 425–429PubMedGoogle Scholar
  70. Masliah E, Mallory M, Alford M, Ge N, Mucke L (1995) Abnormal synaptoc 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
  71. McKee AC, Kosik KS, Kowall NW (1992) Neuritic pathology and dementia in Alzheimer’s disease. Ann Neurol 30: 156–165Google Scholar
  72. 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. Alzheimer Dis Assoc Disord 7: 136–153PubMedGoogle Scholar
  73. 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: 1113–1124PubMedGoogle Scholar
  74. 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: 479–486PubMedGoogle Scholar
  75. Mirra SS, Hart MN, Terry RD (1993) Making the diagnosis of Alzheimer’s disease. Arch Pathol Lab Med 117: 132–144PubMedGoogle Scholar
  76. 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: 303–315PubMedGoogle Scholar
  77. Mirra SS, Gearing M, Heyman A (1994) CERAD guide to the neuropathological assessment of Alzheimer’s disease and other dementias. CERAD, Durham NCGoogle Scholar
  78. Morris JC, McKeel DW Jr, Storandt M, Rubin EM, Price JL, Grant EA, Ball MJ, Berg L (1991) Very mild Alzheimer’s disease: informant-based clinical psychometric and pathological distinction from normal aging. Neurology 41: 469–478PubMedGoogle Scholar
  79. 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: 707–719PubMedGoogle Scholar
  80. Nagy Z, Esiri MM, Cate AM, Smith AD (1997b) Cell cycle markers in the hippocampus in Alzheimer’s disease. Acta Neuropathol 94: 6–15PubMedGoogle Scholar
  81. 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: 165–170PubMedGoogle Scholar
  82. 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: 593Google Scholar
  83. Paulus W, Bancher C, Jellinger K (1992) Interrater reliability in the neuropathologic diagnosis of Alzheimer’s disease. Neurology 42: 329–332PubMedGoogle Scholar
  84. 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: 577Google Scholar
  85. 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: 388–392PubMedGoogle Scholar
  86. Poirier J, Aubert I, Quirion R, Gauthier S, 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
  87. 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
  88. 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: 295–312Google Scholar
  89. 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 twocomponent model. Neurology 44: 2081–2088PubMedGoogle Scholar
  90. 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: 772–778PubMedGoogle Scholar
  91. Scheff SW, Price DA (1993) Synapse loss in the temporal lobe in Alzheimer’s disease. Ann Neurol 33: 190–199PubMedGoogle Scholar
  92. 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: 42–48PubMedGoogle Scholar
  93. Spillantini MG, Bird TD, Ghetti B (1998) Frontotemporal dementia and parkinonism linked to chromosome 17: a new group of tauopathies. Brain Pathol 8: 387–402PubMedGoogle Scholar
  94. Terry RD, Hansen LA, DeTeresa R, Davies P, Tobias H, Katzman R (1987) Senile dementia of the Alzheimer type without neocortical neurofibrillary tangles. J Neuropathol Exp Neurol 46: 262–268PubMedGoogle Scholar
  95. 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: 572–580PubMedGoogle Scholar
  96. Terry RT (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
  97. 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: 356–364Google Scholar
  98. Trojanowski JQ, Shin RW, Schmidt ML, Lee VMY (1995) Relationship between plaques tangles and dystrophic processes in Alzheimers disease. Neurobiol Aging 16: 335–340PubMedGoogle Scholar
  99. 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: 1134–1142PubMedGoogle Scholar
  100. 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: 365–371PubMedGoogle Scholar
  101. 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
  102. 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. Prog Neuropsychopharmacol Biol Psychiatry 19: 1035–1047PubMedGoogle Scholar
  103. Victoroff J, Mack WJ, Lyness SA, Chui HC (1995) Multicenter clinicopathological correlation in dementia. Am J Psychiatry 152: 1476–1484PubMedGoogle Scholar
  104. 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: 548–556PubMedGoogle Scholar
  105. Wilcock GK, Esiri MM (1982) Plaques tangles and dementia. A quantitative study. J Neurol Sci 56: 343–356PubMedGoogle Scholar
  106. Xuereb JH, Gertz HJ, Huppert F, Brayne C, Wischik CM, Mukaetova-Ladinska E (1995) The application of Braak’s staging model of Alzheimer-type pathology to neuropathological diagnosis of dementia (abstr). Neuropathol Appl Neurobiol 21: 44Google Scholar
  107. 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: 291–297PubMedGoogle Scholar

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© Springer-Verlag/Wien 1998

Authors and Affiliations

  • K. A. Jellinger
    • 1
  • C. Bancher
    • 1
  1. 1.Ludwig Boltzmann Institute of Clinical NeurobiologyViennaAustria

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