In addition to senile plaques and cerebral amyloid angiopathy,the hyperphosphorylation of tau protein and formation of intraneuronal neurofibrillary tangles(NFTs)represents another neuropathological hallmark in AD bra...In addition to senile plaques and cerebral amyloid angiopathy,the hyperphosphorylation of tau protein and formation of intraneuronal neurofibrillary tangles(NFTs)represents another neuropathological hallmark in AD brain.Tau is a microtubule-associated protein and localizes predominantly in the axons of neurons with the primary function in maintaining microtubules stability.When the balance between tau phosphorylation and dephosphorylation is changed in favor of the former,tau is hyperphosphorylated and the level of the free tau fractions elevated.The hyperphosphorylation of tau protein and formation of NFTs represent a characteristic neuropathological feature in AD brain.We have discussed the role of Aβin AD in our previous review,this review focused on the recent advances in tau-mediated AD pathology,mainly including tau hyperphosphorylation,propagation of tau pathology and the relationship between tau and Aβ.展开更多
Alzheimer’s disease(AD)is a common neurodegenerative disease characterized clinically by progressive deterioration of memory,and pathologically by histopathological changes including extracellular deposits of amyloid...Alzheimer’s disease(AD)is a common neurodegenerative disease characterized clinically by progressive deterioration of memory,and pathologically by histopathological changes including extracellular deposits of amyloid-beta(A-beta)peptides forming senile plaques(SP)and the intracellular neurofibrillary tangles(NFT)of hyperphosphorylated tau in the brain.This review focused on the new developments of amyloid cascade hypothesis with details on the production,metabolism and clearance of A-beta,and the key roles of some important A-beta-related genes in the pathological processes of AD.The most recent research advances in genetics,neuropathology and pathogenesis of the disease were also discussed.展开更多
基金This work was supported by the grants from the National Natural Science Foundation of China(No.31171019,No.81173108,No.31000574 and No.31200820)the Opening Projects of Shanghai Key Laboratory of Brain Functional Genomics and Key Laboratory of Brain Functional Genomics(East China Normal University),Ministry of Education。
文摘In addition to senile plaques and cerebral amyloid angiopathy,the hyperphosphorylation of tau protein and formation of intraneuronal neurofibrillary tangles(NFTs)represents another neuropathological hallmark in AD brain.Tau is a microtubule-associated protein and localizes predominantly in the axons of neurons with the primary function in maintaining microtubules stability.When the balance between tau phosphorylation and dephosphorylation is changed in favor of the former,tau is hyperphosphorylated and the level of the free tau fractions elevated.The hyperphosphorylation of tau protein and formation of NFTs represent a characteristic neuropathological feature in AD brain.We have discussed the role of Aβin AD in our previous review,this review focused on the recent advances in tau-mediated AD pathology,mainly including tau hyperphosphorylation,propagation of tau pathology and the relationship between tau and Aβ.
基金This work was supported by the grants from the National Natural Science Foundation of China(No.31171019,No.81173108 and No.31000574)the Opening Projects of Shanghai Key Laboratory of Brain Functional Genomics and Key Laboratory of Brain Functional Genomics(East China Normal University),Ministry of Education.
文摘Alzheimer’s disease(AD)is a common neurodegenerative disease characterized clinically by progressive deterioration of memory,and pathologically by histopathological changes including extracellular deposits of amyloid-beta(A-beta)peptides forming senile plaques(SP)and the intracellular neurofibrillary tangles(NFT)of hyperphosphorylated tau in the brain.This review focused on the new developments of amyloid cascade hypothesis with details on the production,metabolism and clearance of A-beta,and the key roles of some important A-beta-related genes in the pathological processes of AD.The most recent research advances in genetics,neuropathology and pathogenesis of the disease were also discussed.