Figure 1.

Multifactorial basis of the pathogenesis of Alzheimer’s disease. Hypotheses regarding genetics (APP/Aβ, apoE4), aging, Aβ, Tau, and inflammation have been promoted to explain this multifactorial disorder. Aβ production increases with APP gene mutations, leading to impairment of neuronal activities. Tau forms neurofibrillary tangles and it impairs synaptic functions. Activated microglia and astroglia are important inflammatory factors in AD. Aging increases oxidative stress and mitochondrial dysfunction, which, in turn, improve Aβ production, Tau hyperphosphorylation, and the generation of inflammation. Comorbidities, such as head injury, diabetes mellitus, and other neurodegeneration diseases, could cause AD.