Yao Pamela J, Zhu Min, Pyun Eunice I, Brooks Andrew I, Therianos Stavros, Meyers Victoria E, Coleman Paul D
Department of Neurobiology & Anatomy, Center for Aging & Developmental Biology, University of Rochester, Rochester, NY 14642, USA.
Neurobiol Dis. 2003 Mar;12(2):97-109. doi: 10.1016/s0969-9961(02)00009-8.
Loss of synapses correlates with cognitive decline in Alzheimer's disease (AD). However, molecular mechanisms underlying the synaptic dysfunction and loss are not well understood. In this study, microarray analysis of brain tissues from five AD cases revealed a reduced expression of a group of related genes, all of which are involved in synaptic vesicle (SV) trafficking. By contrast, several synaptic genes with functions other than vesicle trafficking remained unchanged. Quantitative RT-PCR confirmed and expanded the microarray findings. Furthermore, immunoblotting showed that the protein level of at least one of these gene products, dynamin I, correlated with its reduced transcript. Immunhistochemical analysis exhibited an altered distribution of dynamin I immunolabeling in AD neurons. Microarray analysis of transgenic mice with mutated amyloid precursor protein showed that although the transcript levels for some of the SV trafficking-related genes are also decreased, the change in dynamin did not replicate the AD pattern. The results suggest a link among SV vesicle-trafficking pathways, synaptic malfunction, and AD pathogenesis.
突触丧失与阿尔茨海默病（AD）的认知衰退相关。然而，突触功能障碍和丧失背后的分子机制尚未完全明确。在本研究中，对5例AD患者脑组织进行的微阵列分析显示，一组相关基因的表达降低，所有这些基因都参与突触小泡（SV）运输。相比之下，一些除小泡运输外具有其他功能的突触基因则保持不变。定量逆转录聚合酶链反应（RT-PCR）证实并扩展了微阵列分析结果。此外，免疫印迹显示，这些基因产物中至少一种——发动蛋白I的蛋白质水平与其转录本减少相关。免疫组织化学分析显示，AD神经元中发动蛋白I免疫标记的分布发生改变。对淀粉样前体蛋白突变的转基因小鼠进行的微阵列分析表明，虽然一些与SV运输相关基因的转录水平也降低，但发动蛋白的变化并未重现AD模式。结果表明，SV小泡运输途径、突触功能障碍和AD发病机制之间存在联系。
