阿尔茨海默病( Alzheimer's disease,AD)是一种以记忆障碍、认知功能下降和神经元丢失为特征的神经退行性疾病,其发病机制涉及多种因素,其中 β-淀粉样蛋白(amyloid-BAB)在神经元与体内的代谢异常是关键。Aβ是人类淀粉样前体蛋白(amyloid precursorprotein,APP)经过多种淀粉样蛋白加工途径和非淀粉样蛋白加工途径后的分解产物,并通过脑脊液和组织间液淋巴引流、细胞的清除作用、血脑屏障转运和酶解作用等多种途径进行清除。Aβ的生成和清除是一个动态平衡的过程,其平衡的失调会使 Aβ 在大脑中异常积累导致神经元细胞死亡、突触功能受损和神经元网络改变等,诱发并加剧AD症状。本综述阐述了AD中Aβ的生成、清除和代谢相关机制,总结了AB与神经元、星形胶质细胞、尿素循环等的相互作用机制,为进一步发现新的AD诊断及治疗靶点提供新思路。

Alzheimer's disease (AD)is a neurodegenerative disorder characterized by memoryimpairment, cognitive decline and neuronal loss. Its pathogenesis involves a variety offactors, among which amyloid-β (Aβ) is critical in neurons and the body. Aβ is thedecomposition product of human amyloid precursor protein(APP) through various amyloidprocessing routes and non-amyloid processing routes, and is cleared through various wayssuch as cerebrospinal fuid and inter-tissue fluid lymphatic drainage, cell clearance, bloodand brain barrier transport and enzymatic hydrolysis. The generation and clearance of Aβ is a dyamic and balanced process, and the imbalance of its balance will accumulate Aβ in the brain, leading to neuronal cell death, impaired synaptic function and neuronalnetwork changes, inducing and exacerbate AD symptoms. This review expounded themechanisms of Aβ generation, clearance and metabolism in AD, summarized theinteraction mechanisms of Aβ with neurons, astrocytes, urea cycle, etc, and provided newideas for further discovery of new therapeutic and diagnostic targets for AD.