Sze C I, Troncoso J C, Kawas C, Mouton P, Price D L, Martin L J
Department of Pathology, University of Colorado Health Science Center, Denver, USA.
J Neuropathol Exp Neurol. 1997 Aug;56(8):933-44. doi: 10.1097/00005072-199708000-00011.
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.
阿尔茨海默病（AD）患者海马体中的突触缺陷与认知障碍的严重程度相关。我们研究了三个尸检组：认知正常且稳定的对照组；具有诊断为可能AD（p-AD）的老年斑密度以及早期AD特征性神经原纤维变化（Braak分期III期）的认知未受损受试者；以及具有明确AD和早期至重度AD典型神经原纤维变化（Braak分期III、V或VI期）的个体。通过对从海马体、内嗅皮质、尾状核和枕叶皮质分离的突触膜组分进行免疫印迹，对突触素（一种突触前囊泡蛋白）水平进行定量。将明确AD组与对照组相比（降低55%，p<0.0001）、p-AD组与对照组相比（降低25%，p<0.005）、明确AD组与p-AD组相比（降低30%，p<0.05）时，海马体中突触素的平均水平降低，但内嗅皮质、枕叶皮质和尾状核中的水平要么未改变，要么与海马体相比变化不那么显著。通过单变量分析，海马体突触素水平与神经心理学测量结果相关，包括简易精神状态检查评分（r = 0.83，p<0.0001）和Blessed评分（r = 0.74，P<0.001），还与老年斑密度相关（r = 0.89，p<0.0001）。我们得出结论，AD患者海马体中的突触异常与神经病理学的严重程度和记忆缺陷相关，并且这种缺陷可能在AD早期认知障碍的神经心理学证据出现之前就已存在。
