Dear Editor,Brain-reactive autoantibodies are thought to play an important role in mediating disorders of the central nervous system(CNS).These antibodies direct the processes underlying several diseases,such as multi...Dear Editor,Brain-reactive autoantibodies are thought to play an important role in mediating disorders of the central nervous system(CNS).These antibodies direct the processes underlying several diseases,such as multiple sclerosis(MS),neuromyelitis optica(NMO),and neuropsychiatric systemic lupus erythematosus[1-3].In infectious diseases of the CNS,the pathogen itself is regarded to play a major role in the pathogenesis[4].展开更多
Increased neuronal apoptosis is an important pathological feature of Alzheimer’s disease(AD).The Bcl-2-interacting mediator of cell death(Bim)mediates amyloid-beta(Aβ)-induced neuronal apoptosis.Naturally-occurring ...Increased neuronal apoptosis is an important pathological feature of Alzheimer’s disease(AD).The Bcl-2-interacting mediator of cell death(Bim)mediates amyloid-beta(Aβ)-induced neuronal apoptosis.Naturally-occurring antibodies against Bim(NAbs-Bim)exist in human blood,with their levels and functions unknown in AD.In this study,we found that circulating NAbs-Bim were decreased in AD patients.Plasma levels of NAbs-Bim were negatively associated with brain amyloid burden and positively associated with cognitive functions.Furthermore,NAbs-Bim purified from intravenous immunoglobulin rescued the behavioral deficits and ameliorated Aβdeposition,tau hyperphosphorylation,microgliosis,and neuronal apoptosis in APP/PS1 mice.In vitro investigations demonstrated that NAbs-Bim were neuroprotective against AD through neutralizing Bim-directed neuronal apoptosis and the amyloidogenic processing of amyloid precursor protein.These findings indicate that the decrease of NAbs-Bim might contribute to the pathogenesis of AD and immunotherapies targeting Bim hold promise for the treatment of AD.展开更多
Dear Editor,Alzheimer’s disease(AD)is the most common cause of dementia among the older population,and is characterized by amyloid-beta(Aβ)accumulation,hyperphosphorylation of tau,and finally neurodegeneration in th...Dear Editor,Alzheimer’s disease(AD)is the most common cause of dementia among the older population,and is characterized by amyloid-beta(Aβ)accumulation,hyperphosphorylation of tau,and finally neurodegeneration in the brain[1].Aβ is the major pathological agent in AD,thus currently most efforts in developing therapies for AD target this peptide.The most promising therapy for this disease is immunotherapy.展开更多
基金supported by the National Natural Science Foundation of China(81600936 and 81701046)the Natural Science Foundation of Chongqing Municipality,China(cstc2018jcyJAX0511)。
文摘Dear Editor,Brain-reactive autoantibodies are thought to play an important role in mediating disorders of the central nervous system(CNS).These antibodies direct the processes underlying several diseases,such as multiple sclerosis(MS),neuromyelitis optica(NMO),and neuropsychiatric systemic lupus erythematosus[1-3].In infectious diseases of the CNS,the pathogen itself is regarded to play a major role in the pathogenesis[4].
基金supported by the National Natural Science Foundation of China(81930028,81971024,and 81971033).
文摘Increased neuronal apoptosis is an important pathological feature of Alzheimer’s disease(AD).The Bcl-2-interacting mediator of cell death(Bim)mediates amyloid-beta(Aβ)-induced neuronal apoptosis.Naturally-occurring antibodies against Bim(NAbs-Bim)exist in human blood,with their levels and functions unknown in AD.In this study,we found that circulating NAbs-Bim were decreased in AD patients.Plasma levels of NAbs-Bim were negatively associated with brain amyloid burden and positively associated with cognitive functions.Furthermore,NAbs-Bim purified from intravenous immunoglobulin rescued the behavioral deficits and ameliorated Aβdeposition,tau hyperphosphorylation,microgliosis,and neuronal apoptosis in APP/PS1 mice.In vitro investigations demonstrated that NAbs-Bim were neuroprotective against AD through neutralizing Bim-directed neuronal apoptosis and the amyloidogenic processing of amyloid precursor protein.These findings indicate that the decrease of NAbs-Bim might contribute to the pathogenesis of AD and immunotherapies targeting Bim hold promise for the treatment of AD.
基金This work was supported by the National Natural Science Foundation of China(81701046)Chongqing Science and Technology Commission(cstc2018jcyjAX0664).
文摘Dear Editor,Alzheimer’s disease(AD)is the most common cause of dementia among the older population,and is characterized by amyloid-beta(Aβ)accumulation,hyperphosphorylation of tau,and finally neurodegeneration in the brain[1].Aβ is the major pathological agent in AD,thus currently most efforts in developing therapies for AD target this peptide.The most promising therapy for this disease is immunotherapy.
