老年痴呆症中神经递质释放异常的机理

阿尔茨海默症(Alzheimer’s disease,AD)是以胞外淀粉样蛋白(amyloid-β,Aβ)沉积和胞内神经纤维缠结为病理特征的神经退行性疾病。AD典型症状的出现与中枢神经系统突触数量的减少密切相关,因此,明确AD早期突触数量还没有明显降低时突触功能失调的机制对AD的临床诊治具有十分重要的意义。寡聚Aβ、早老素功能缺失等因素造成的突触前神经递质释放异常很有可能是AD突触功能异常的上游机制。对AD中神经递质释放异常的现象和机制进行综述,并对这一领域存在的开放问题作一归纳。

Abnormal neurotransmitter release in Alzheimer＇s disease

Alzheimer＇s disease （AD） is a severe neurodegenerative disease that is characterized by the presence of extracellular amyloid-β （Aβ） plaques and intracellular neurofibrillary tangles. Synapse loss is the best pathological correlate of typical AD symptoms, but once synapse loss is observed in patients with AD, its progression is hard to be stopped. Thus, elucidating synapse dysfunction before the occurrence of central synapse loss is of particular importance to the diagnosis and treatment of AD. Aberrant neurotransmitter release, caused by Aβ oligomers, loss- of-function presenilin mutations, etc, is possibly a promising upstream mechanism of synapse dysfunction. In this review, we first describe presynaptic transmitter release abnormalities and underlying mechanisms in AD, and then raise a few key open questions in the research field.