Loss of the presynaptic vesicle protein synaptophysin in hippocampus correlates with cognitive decline in Alzheimer disease

被引:477
作者
Sze, CI
Troncoso, JC
Kawas, C
Mouton, P
Price, DL
Martin, LJ
机构
[1] JOHNS HOPKINS UNIV,SCH MED,NEUROPATHOL LAB,DEPT PATHOL,BALTIMORE,MD 21205
[2] JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205
[3] JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205
[4] JOHNS HOPKINS UNIV,SCH MED,CTR GERONTOL RES,BALTIMORE,MD 21205
[5] JOHNS HOPKINS UNIV,SCH MED,ALZHEIMERS DIS RES CTR,BALTIMORE,MD 21205
[6] UNIV COLORADO,HLTH SCI CTR,DEPT PATHOL,DENVER,CO 80262
关键词
Braak stage; CA1; memory loss; senile plaque; synapse;
D O I
10.1097/00005072-199708000-00011
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
We tested the hypothesis that synaptic defects in the hippocampus of individuals with Alzheimer disease (AD) correlate with the severity of cognitive impairment. Three postmortem groups were studied: controls with normal and stable cognition; cognitively intact subjects with senile plaque densities diagnostic for possible AD (p-AD) and neurofibrillary changes characteristic of early AD (Braak stage III); and individuals with definite AD and neurofibrillary changes typical of incipient to severe AD (Braak stage III, V, or VI). Synaptophysin (a presynaptic vesicle protein) levels were quantified by immunoblotting of synaptic membrane fractions isolated from hippocampus, entorhinal cortex, caudate nucleus, and occipital cortex. Average synaptophysin levels were reduced in hippocampus when comparing definite AD to controls (55%, p < 0.0001), p-AD to control (25%, p < 0.005), and definite AD to p-AD (30%, p < 0.05), but levels in entorhinal cortex, occipital cortex, and caudate nucleus were either unchanged or less significantly altered than in hippocampus. By univariate analysis, hippocampal synaptophysin levels correlated with neuropsychological measurements, including Mini-mental state examination scores (r = 0.83, p < 0.0001) and Blessed scores (r = 0.74, P < 0.001), and with senile plaque densities (r = 0.89, p < 0.0001). We conclude that synaptic abnormalities in the hippocampus correlate with the severity of neuropathology and memory deficit in individuals with AD, and that this defect may predate neuropsychological evidence for cognitive impairment early in AD.
引用
收藏
页码:933 / 944
页数:12
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