[Alzheimer disease. Epidemiology, genetics and physiopathological hypotheses]

Aging is the chief risk factor for Alzheimer's disease (AD). Other risk factors are aluminum in drinking water, diabetes mellitus, head trauma. Protective factors are: higher education, cigarette smoking, nonsteroidal anti-inflammatory drugs and estrogen use.

Mutations of presenilins 1 and 2 and of the APP gene in families with early-onset AD. Apolipoprotein E polymorphism in late-onset familial and sporadic AD.

Amyloid deposits in senile plaques and therefore dementia could be due to an overproduction of Abeta (Down's syndrome) or due to the primary (APP mutation) or secondary (role of diabetes, mellitus, apoE polymorphism: protective effect of estrogen) abnormal neurotoxic feature of Abeta. The hyperphosphorylation of tau (a protein which plays a pivotal role in the axonal transport), perhaps regulated by the apoE polymorphism could lead to neurofibrillar degeneration. Neurotoxic mediators produced by the activated microglia (perhaps activated by neuronal damage) and oxidative stress could also be involved in the neurodegeneration.