Alzheimer's disease(AD)is a neurodegenerative disease characterized by progressive cognitive decline,accompanied by amyloid-β(Aβ)overload and hyperphosphorylated tau accumulation in the brain.Synaptic dysfunctio...Alzheimer's disease(AD)is a neurodegenerative disease characterized by progressive cognitive decline,accompanied by amyloid-β(Aβ)overload and hyperphosphorylated tau accumulation in the brain.Synaptic dysfunction,an important pathological hallmark in AD;is recognized as the main cause of the cognitive impairments.Accumulating evidence suggests that synaptic dysfunction could be an early pathological event in AD.Pathological tau,which is detached from axonal microtubules and mislocalized into pre-and postsynaptic neuronal compartments,is suggested to induce synaptic dysfunction in several ways,including reducing mobility and release of presynaptic vesicles,decreasing glutamatergic receptors,impairing the maturation of dendritic spines at postsynaptic terminals,disrupting mitochondrial transport and function in synapses,and promoting the phagocytosis of synapses by microglia.Here,we review the current understanding of how pathological tau mediates synaptic dysfunction and contributes to cognitive decline in AD.We propose that elucidating the mechanism by which pathological tau impairs synaptic function is essential for exploring novel therapeutic strategies for AD.展开更多
基金supported partially by the National Natural Science Foundation of China(82030032,32070960,81871108 to DL,81760221 and 81960221 to XPY,and 81660209 to ZYC)the National Science&Technology Fundamental Resource Investigation Program of China(2018FY100903 to XPY)Science and Technology Project Founded by the Education Department of Jiangxi Province(GJJ201834 to MXW).
文摘Alzheimer's disease(AD)is a neurodegenerative disease characterized by progressive cognitive decline,accompanied by amyloid-β(Aβ)overload and hyperphosphorylated tau accumulation in the brain.Synaptic dysfunction,an important pathological hallmark in AD;is recognized as the main cause of the cognitive impairments.Accumulating evidence suggests that synaptic dysfunction could be an early pathological event in AD.Pathological tau,which is detached from axonal microtubules and mislocalized into pre-and postsynaptic neuronal compartments,is suggested to induce synaptic dysfunction in several ways,including reducing mobility and release of presynaptic vesicles,decreasing glutamatergic receptors,impairing the maturation of dendritic spines at postsynaptic terminals,disrupting mitochondrial transport and function in synapses,and promoting the phagocytosis of synapses by microglia.Here,we review the current understanding of how pathological tau mediates synaptic dysfunction and contributes to cognitive decline in AD.We propose that elucidating the mechanism by which pathological tau impairs synaptic function is essential for exploring novel therapeutic strategies for AD.
