Two of the most common causes of dementia are Alzheimer’s disease(AD)and frontotemporal dementia(FTD).AD is an irreversible,progressive neurodegenerative disorder that is clinically characterized by severe memory los...Two of the most common causes of dementia are Alzheimer’s disease(AD)and frontotemporal dementia(FTD).AD is an irreversible,progressive neurodegenerative disorder that is clinically characterized by severe memory loss and behavioral impairment that eventually interferes with everyday function.AD is neuropathologically defined by the presence of extracellularβ-amyloid plaques and intracellular accumulation of neurofibrillary tangles(NFTs)that primarily contain aggregated,hyperphosphorylated tau(pTau).Intriguingly,pTau is also the central protein in multiple subtypes of FTD(e.g.corticobasal degeneration,progressive supranuclear palsy,Pick’s disease).FTD is an umbrella term for a group of neurological conditions that primarily affect the temporal and frontal regions of the brain.Mutations in the tau gene(MAPT)can cause familial FTD,providing further evidence of the integral role of tau in FTD.Physiologically,tau regulates microtubule structure and dynamics,as well as axonal transport through interaction with tubulin.Tau is also involved in neuronal development and synaptogenesis.In AD and FTD,tau becomes hyperphosphorylated and undergoes major conformational changes,causing it to aggregate into the characteristic neuropathological lesions that define AD and FTD.Despite the known involvement of tau in these diseases,exactly how tau mediates toxicity is still unclear.展开更多
基金supported by funding from the Bluesand Foundation and Dementia Australia to ED,and Philippe Chatrier Foundation to GP.
文摘Two of the most common causes of dementia are Alzheimer’s disease(AD)and frontotemporal dementia(FTD).AD is an irreversible,progressive neurodegenerative disorder that is clinically characterized by severe memory loss and behavioral impairment that eventually interferes with everyday function.AD is neuropathologically defined by the presence of extracellularβ-amyloid plaques and intracellular accumulation of neurofibrillary tangles(NFTs)that primarily contain aggregated,hyperphosphorylated tau(pTau).Intriguingly,pTau is also the central protein in multiple subtypes of FTD(e.g.corticobasal degeneration,progressive supranuclear palsy,Pick’s disease).FTD is an umbrella term for a group of neurological conditions that primarily affect the temporal and frontal regions of the brain.Mutations in the tau gene(MAPT)can cause familial FTD,providing further evidence of the integral role of tau in FTD.Physiologically,tau regulates microtubule structure and dynamics,as well as axonal transport through interaction with tubulin.Tau is also involved in neuronal development and synaptogenesis.In AD and FTD,tau becomes hyperphosphorylated and undergoes major conformational changes,causing it to aggregate into the characteristic neuropathological lesions that define AD and FTD.Despite the known involvement of tau in these diseases,exactly how tau mediates toxicity is still unclear.
