DHA-PC and PSD-95 decrease after loss of synaptophysin and before neuronal loss in patients with Alzheimer's disease.
DHA-PC and PSD-95 decrease after loss of synaptophysin and before neuronal loss in patients with Alzheimer's disease.
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DOI：
10.1038/srep07130
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发表时间：
2014-11-20
影响因子：
4.6
通讯作者：
Setou M
中科院分区：
文献类型：
--
作者：
Yuki D;Sugiura Y;Zaima N;Akatsu H;Takei S;Yao I;Maesako M;Kinoshita A;Yamamoto T;Kon R;Sugiyama K;Setou M
阿尔茨海默病（Alzheimer's disease，AD）是一种以老年斑、神经元缠结、突触破坏和神经元丢失为特征的进行性神经退行性疾病。几项研究已经证明AD脑中含二十二碳六烯酸的磷脂酰胆碱（DHA-PC）减少。在这项研究中，我们使用基质辅助激光解吸/电离成像质谱在死后AD脑显示，PC分子物种含有硬脂酸和DHA，即PC（18：0/22：6），选择性地耗尽在AD患者的灰质。此外，在具有显著淀粉样蛋白β（Aβ）沉积的脑区中，PC（18：0/22：6）减少的幅度与疾病持续时间显著相关。此外，在分子水平上，这种消耗与突触后蛋白PSD-95的水平降低有关，但与突触前蛋白突触素无关。有趣的是，PC（18：0/22：6）水平的降低与AD中Aβ沉积和神经元丢失的程度无关。相关分析显示，各因素对病程的影响顺序为Aβ沉积、突触前破坏、突触后破坏伴PC（18：0/22：6）减少、神经元丢失。
Alzheimer's disease (AD) is a progressive neurodegenerative disease that is characterized by senile plaques, neurofibrillary tangles, synaptic disruption, and neuronal loss. Several studies have demonstrated decreases of docosahexaenoic acid-containing phosphatidylcholines (DHA-PCs) in the AD brain. In this study, we used matrix-assisted laser desorption/ionization imaging mass spectrometry in postmortem AD brain to show that PC molecular species containing stearate and DHA, namely PC(18:0/22:6), was selectively depleted in the gray matter of patients with AD. Moreover, in the brain regions with marked amyloid β (Aβ) deposition, the magnitude of the PC(18:0/22:6) reduction significantly correlated with disease duration. Furthermore, at the molecular level, this depletion was associated with reduced levels of the postsynaptic protein PSD-95 but not the presynaptic protein synaptophysin. Interestingly, this reduction in PC(18:0/22:6) levels did not correlate with the degrees of Aβ deposition and neuronal loss in AD. The analysis of the correlations of key factors and disease duration showed that their effects on the disease time course were arranged in order as Aβ deposition, presynaptic disruption, postsynaptic disruption coupled with PC(18:0/22:6) reduction, and neuronal loss.