Decreased Levels of PSD95 and Two Associated Proteins and Increased Levels of BCl2 and Caspase 3 in Hippocampus from Subjects with Amnestic Mild Cognitive Impairment: Insights into Their Potential Roles for Loss of Synapses and Memory, Accumulation of Aβ, and Neurodegeneration in a Prodromal Stage of Alzheimer's Disease
Decreased Levels of PSD95 and Two Associated Proteins and Increased Levels of BCl2 and Caspase 3 in Hippocampus from Subjects with Amnestic Mild Cognitive Impairment: Insights into Their Potential Roles for Loss of Synapses and Memory, Accumulation of Aβ, and Neurodegeneration in a Prodromal Stage of Alzheimer's Disease
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DOI：
10.1002/jnr.22227
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发表时间：
2010-02-15
影响因子：
4.2
通讯作者：
Butterfield, D. Allan
中科院分区：
文献类型：
--
作者：
Sultana, Rukhsana;Banks, William A.;Butterfield, D. Allan
阿尔茨海默病（AD）是最常见的痴呆形式，其病理特征在于老年斑、神经元缠结、突触破坏和丧失以及进行性神经元缺陷。AD发病机制的确切机制在很大程度上仍然未知。随着技术的进步，被称为遗忘型轻度认知障碍（MCI）的AD前阶段的诊断已经成为可能。遗忘型MCI的临床特征是记忆障碍，但日常生活活动正常，无痴呆。在本研究中，与对照组相比，我们观察到MCI受试者海马中关键突触蛋白PSD 95的水平显著降低，并且与PSD 95相关的两种蛋白质N-甲基-D-天冬氨酸受体亚基2A（NR 2A）和低密度脂蛋白受体-1（LRP 1）的水平也降低。PSD 95和NR 2A参与长时程增强，这是记忆形成的关键成分，LRP 1参与淀粉样β肽的流出（1-42）。可以想象，β（1-42）对MCI和AD的发病机制至关重要，包括两种情况下大脑存在的氧化应激。从目前的研究中获得的数据表明，这些蛋白质可能参与突触改变，细胞凋亡和随之而来的递减在学习和记忆与MCI到AD的进展。(C)2009 Wiley-Liss，Inc.
Alzheimer's disease (AD) is the most common form of dementia and is pathologically characterized by senile plaques, neurofibrillary tangles, synaptic disruption and loss, and progressive neuronal deficits. The exact mechanism(s) of AD pathogenesis largely remain unknown. With advances in technology diagnosis of a pre-AD stage referred to as amnestic mild cognitive impairment (MCI) has become possible. Amnestic MCI is characterized clinically by memory deficit, but normal activities of daily living and no dementia. In the present study, compared to controls, we observed in hippocampus from subjects with MCI a significantly decreased level of PSD95, a key synaptic protein, and also decreased levels of two proteins associated with PSD95, the N-methyl-D-aspartate receptor, subunit 2A (NR2A) and the low-density lipoprotein receptor-1 (LRP1). PSD95 and NR2A are involved in long-term potentiation, a key component of memory formation, and LRP1 is involved in efflux of amyloid beta-peptide (1-42). A beta (1-42) conceivably is critical to the pathogenesis of MCI and AD, including the oxidative stress under which brain in both conditions exist. The data obtained from the current study suggest a possible involvement of these proteins in synaptic alterations, apoptosis and consequent decrements in learning and memory associated with the progression of MCI to AD. (C) 2009 Wiley-Liss, Inc.