Sze C I, Bi H, Kleinschmidt-DeMasters B K, Filley C M, Martin L J
Department of Pathology, University of Colorado Health Sciences Center, B-216, 4200 East Ninth Ave., Denver, CO 80262, USA.
J Neurol Sci. 2000 Apr 15;175(2):81-90. doi: 10.1016/s0022-510x(00)00285-9.
We tested whether regional or selective alterations in presynaptic proteins occur in Alzheimer's disease (AD) and correlate with tests of cognitive function. We measured the levels of seven presynaptic proteins (synaptobrevin, synaptotagmin, SNAP-25, syntaxin, SV2, Rab3a, and synapsin I) by immunoblotting in postmortem tissue from four brain regions (hippocampus, entorhinal cortex, caudate nucleus, and occipital cortex). Three subject groups were studied: AD, possible/early AD (p-AD), and age-matched controls. Synaptobrevin and synaptotagmin were significantly reduced (29%, P<0.08; 38%, P<0. 07) in hippocampus in p-AD compared to controls. In definite AD compared to controls, selective regional reductions in vesicle proteins were found: synaptobrevin (46%, P<0.05), synaptotagmin (52%, P<0.01), and Rab3a (30%, P<0.05) in hippocampus; synaptobrevin (31%, P<0.01), synaptotagmin (15%, P<0.05), and Rab3a (44%, P<0.05) in entorhinal cortex. In contrast, the levels of two vesicle proteins (synapsin I and SV2) and two presynaptic membrane proteins (syntaxin and SNAP-25) were similar to controls. Synaptobrevin was the only vesicle protein reduced in AD in all four brain regions (occipital cortex 37%, P<0.05; caudate nucleus 31%, P<0.05). By univariate analysis of all cases, Mini-Mental State Examination, Blessed (BIMC) and Free Recall scores were strongly correlated with reduced levels of synaptic vesicle proteins synaptobrevin, synaptotagmin, and Rab3a in hippocampus and entorhinal cortex. These results suggest that there are selective and early defects in presynaptic vesicle proteins, but not synaptic plasma membrane proteins in AD and that defects correlate with cognitive dysfunction in this disease.
我们测试了阿尔茨海默病（AD）中突触前蛋白是否存在区域性或选择性改变，以及这些改变是否与认知功能测试相关。我们通过免疫印迹法测量了来自四个脑区（海马体、内嗅皮质、尾状核和枕叶皮质）的尸检组织中七种突触前蛋白（突触小泡蛋白、突触结合蛋白、SNAP-25、 syntaxin、SV2、Rab3a和突触素I）的水平。研究了三个受试者组：AD组、可能/早期AD（p-AD）组和年龄匹配的对照组。与对照组相比，p-AD组海马体中的突触小泡蛋白和突触结合蛋白显著减少（分别为29%，P<0.08；38%，P<0.07）。与对照组相比，确诊AD组中发现囊泡蛋白存在选择性区域性减少：海马体中的突触小泡蛋白（46%，P<0.05）、突触结合蛋白（52%，P<0.01）和Rab3a（30%，P<0.05）；内嗅皮质中的突触小泡蛋白（31%，P<0.01）、突触结合蛋白（15%，P<0.05）和Rab3a（44%，P<0.05）。相比之下，两种囊泡蛋白（突触素I和SV2）以及两种突触前膜蛋白（syntaxin和SNAP-25）的水平与对照组相似。突触小泡蛋白是AD中所有四个脑区唯一减少的囊泡蛋白（枕叶皮质减少37%，P<0.05；尾状核减少31%，P<0.05）。对所有病例进行单因素分析发现，简易精神状态检查表、Blessed（BIMC）和自由回忆得分与海马体和内嗅皮质中突触囊泡蛋白突触小泡蛋白、突触结合蛋白和Rab3a水平的降低密切相关。这些结果表明，AD中突触前囊泡蛋白存在选择性和早期缺陷，但突触质膜蛋白不存在缺陷，且这些缺陷与该疾病的认知功能障碍相关。
