Amyloid-Beta and Phosphorylated Tau Accumulations Cause Abnormalities at Synapses of Alzheimer's disease Neurons.
Amyloid-Beta and Phosphorylated Tau Accumulations Cause Abnormalities at Synapses of Alzheimer's disease Neurons.
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DOI：
10.3233/jad-160612
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Reddy PH
中科院分区：
文献类型：
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作者：
Rajmohan R;Reddy PH
淀粉样β蛋白(Aβ)和过度磷酸化的tau是阿尔茨海默病(AD)的标志性病变。然而，突触丢失和神经传递功能障碍更直接地与疾病严重程度有关。这些病变在疾病的病因学进展中的作用仍然存在争议。生化、细胞、分子和病理学研究提供了几条证据，并提高了我们对淀粉样β蛋白和过度磷酸化tau积累如何直接损害突触和改变神经传递的理解。体外证据表明，淀粉样β蛋白和过度磷酸化的tau具有直接和间接的细胞毒性作用，影响神经传递、轴突运输、信号级联、细胞器功能和免疫反应，从而导致突触丢失和神经递质释放功能障碍。临床前模型和尸检研究的观察支持这些发现，表明虽然阳性病变的病因学仍然难以捉摸，但移除它们可能会降低疾病的严重性和进展。这篇文章的目的是强调进一步研究tau在疾病进展中的作用及其与Aβ和神经递质的相互作用的必要性。
Amyloid Beta (Aβ) and hyperphosphorylated tau are hallmark lesions of Alzheimer disease (AD). However, the loss of synapses and dysfunctions of neurotransmission are more directly tied to disease severity. The role of these lesions in the pathoetiological progression of the disease remains contested. Biochemical, cellular, molecular and pathological studies provided several lines of evidence and improved our understanding of how amyloid beta and hyperphosphorylated tau accumulation may directly harm synapses and alter neurotransmission. In-vitro evidence suggests that amyloid beta and hyperphosphorylated tau have both direct and indirect cytotoxic effects that affect neurotransmission, axonal transport, signaling cascades, organelle function, and immune response in ways that lead to synaptic loss and dysfunctions in neurotransmitter release. Observations in preclinical models and autopsy studies support these findings, suggesting that while the pathoetiology of positive lesions remains elusive, their removal may reduce disease severity and progression. The purpose of this article is to highlight the need for further investigation of the role of tau in disease progression and its interactions with Aβ and neurotransmitters alike.