Neurobiological mechanisms involved in the pathogenesis of Alzheimer’s disease

摘要: Alzheimer’s disease (AD) is one of the many neurodegenerative disorders which is characterized by progressive loss of neurons due to the extracellular accumulation of misprocessed and aggregated amyloid beta (Aβ)-plaques and appearance of intracellular neurofibrillary tangles containing hyperphosphorylated tau protein which ultimately leads to loss of synapses and cognitive decline. Aggregation of amyloid beta (Aβ)-plaques is the hallmark of AD. Aβ is the proteolytic cleavage product of amyloid precursor protein (APP) which is cleaved by β- and γ-secretase enzymes into Aβ1–42 and Aβ1–40 isoforms where the former readily aggregate more rapidly than the latter. Tau protein, the major component of neurofibrillary tangles, is a microtubule-associated protein which is usually soluble but becomes insoluble as it forms tangles of oligomers which is thought to be initiated by toxic concentrations of Aβ …