Summary
Whereas the number of cortical neurons in human brain does not significantly change with age, there is a significant reduction of synaptic terminals in both normal aging brain and Alzheimer’s disease (AD). Multivariant analysis of a cohort of AD patients showed a highly significant correlation between psychostatus and reduction of midfrontal synapses and large neurons, while there was no correlation with amyloid deposits. Another variable contributing to cognitive decline are numbers or neurofibrillary tangles and neuron loss in the cholinergic nucleus basalis of Meynert These and other recent morphologic data do not support the hypothesis that amyloid deposition is a major pathogenic factor of both neuronal and synaptic loss in aging and AD. The causes of synaptic pathology in AD remain to be elucidated.
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Alford MF, Masliah E, Hansen LA, Terry RD (1993) A simple dot-immunobinding assay for the quantification of synaptophysin-like immunoreactivity in the human brain. J Histochem Cytochem 42:283–287.
Blanks JC, Hinton DR, Sandun AA, Miller CA (1989) Retinal ganglion cell degeneration in Alzheimer’s disease. Brain Res 501:364–372.
Blessed G, Tomlinson BE, Roth M (1988) The association between quantitative measures of dementia and of senile changes in the cerebral grey matter of elderly subjects. Br J Psychiatry 114:797–811.
Brody H (1955) Organization of the cerebral cortex. III. A study of aging in the human cerebral cortex. J Comp Neurol 102:511–556.
Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, Roses AD, Haines JL, Peicak-Vance MA (1993) Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science 261:921–923.
Cotman CW, Cummings BJ, Whitson (1991) The role of misdirect plasticity in plaque biogenesis and Alzheimer’s disease pathology. In: Hefti F, Brachet P, Will B, Christen Y (eds) Growth factors and Alzheimer’s disease. Springer, New York, pp 222–233.
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 12:189–198.
Fuld PA (1978) Psychological testing in the differential diagnosis of the dementia. In: Katzman R, Terry RD, Bick KL (eds) Alzheimer’s disease: senile dementia and related diseases. Raven Press, New York, pp 185–196.
Hamos JE, DeGennaro LJ, Drachman DA (1989) Synaptic loss in Alzheimer’s disease and other dementias. Neurology 39:344–361.
Hansen LA, DeTeresa R, Davies P, Terry R (1988) Neocortical morphometry, lesion counts, and choline acetyltransferase levels in the age spectrum of Alzheimer’s disease. Neurology 38:48–54.
Hyman BT, Marzloff K, Arriagada PV (1993) Lack of accumulation of senile plaques or amyloid burden in aging, Alzheimer’s disease and Down syndrome (Abstract). J Neuropathol Exp Neurol 52:264.
Hyman BT, Van Hoesen GW, Damasio AR, Barnes CL (1984) Alzheimer’s disease: cell-specific pathology isolates the hippocampal formation. Science 225:1168–1170.
Ihara Y (1988) Massive somatodendritic sprouting of cortical neurons in Alzheimer’s disease. Brain Res 459:138–144.
Masliah E, Fagan AM, Terry RD, DeTeresa R, Mallory M, Gage FH (1991a) Reactive synaptogenesis assessed by synaptophysin immunoreactivity is associated with GAP-43 in the dentate gyrus of the adult rat. Exp Neurol 113:131–142.
Masliah E, Mallory M, Hansen L, Alford M, Albright T, DeTeresa R, Terry RD, Baudier J, Saitoh T (1991b) Patterns of aberrant sprouting in Alzheimer disease. Neuron 6:729–739.
Masliah E, Mallory M, Hansen L, Alford M, DeTeresa R, Terry R, Baudier J, Saitoh T (1992) Localization of amyloid precursor protein in GAP43-immunoreactive aberrant sprouting neuntes in Alzheimer’s disease. Brain Res 574:312–316.
Masliah E, Terry RD, Alford M, DeTeresa R (1990) Quantitative immunohistochemistry of synaptophysin in human neocortex: an alternative method to estimate density of presynaptic terminals in paraffin sections. J Histochem Cytochem 38:837–844.
Masliah E, Terry RD, Alford M, DeTeresa RM, Hansen LA (1991c) Cortical and subcortical patterns of synaptophysin-like immunoreactivity in Alzheimer disease. Am J Pathol 183:235–246.
Mattis S (1991) Mental status examination for organic mental syndrome in the elderly patients. In: Bellack L, Karasu TB (eds) Geriatric psychiatry. Grune and Stratton, New York, pp 77–121.
Podlisny MB, Stephenson DT, Frosch MP, Tolan DR, Lieberburg I, Clemens JA, Selkoe DJ (1993) Microinjection of synthetic amyloid β-protein in monkey cerebral cortex fails to produce acute neurotoxicity. Am J Pathol 142:17–24.
Samuel W, Terry RD, DeTeresa R, Butters N, Masliah E (1994) Clinical correlates of cortical and nucleus basalis pathology in Alzheimer dementia. Arch Neurol 51:772–778.
Scheff SW, Price DA (1993) Synapse loss in the temporal lobe in Alzheimer’s disease. Ann Neurol 33:190–199.
Strubel RG, Clark HB (1992) Olfactory bulb lesions in Alzheimer’s disease. Neurobiol Aging 13:469–473.
Terry RD, DeTeresa R, Hansen LA (1987) Neocortical cell counts in normal human adult aging. Ann Neurol 21:530–539.
Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R, Hill R, Hansen LA, Katzman R (1991) Physical basis of cognitive alterations in Alzheimer disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol 30:572–580.
Verano A, Chandran R, Faraldi F, Bennet D, Reyes MG (1990) Volume density of senile plaques in Alzheimer’s disease (Abstract). J Neuropathol Exp Neurol 52:264.
Yankner BA, Duffy LK, Kirschner DA (1990) Neurotrophic and neurotoxic effects of amyloid β protein: reversal by tachykinin neuropeptides. Science 250:279–282.
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© 1994 Springer-Verlag/Wien
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Terry, R.D., Masliah, E. (1994). Synaptic pathology in the pathogenesis of Alzheimer dementia. In: Jellinger, K.A., Ladurner, G., Windisch, M. (eds) New Trends in the Diagnosis and Therapy of Alzheimer’s Disease. Key Topics in Brain Research. Springer, Vienna. https://doi.org/10.1007/978-3-7091-9376-1_1
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DOI: https://doi.org/10.1007/978-3-7091-9376-1_1
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