Alzheimer's disease: molecular concepts and therapeutic targets

The beta amyloid peptide is the major component of the neuritic plaques, th e characteristic lesions in Alzheimer's disease. Mutations in three genes ( APP, PS-1, and PS-2) cause familial Alzheimer's disease by alteration of th e rate of generation of amyloid peptide or the length of this peptide. Howe ver, in the 90% nonfamilial cases, other factors play a major pathogenetic role. These include the apolipoprotein E genotype, the "plaque-associated" proteins promoting the formation of toxic fibrillar aggregates or the chron ic inflammatory responses. The aim of this review is to explain the steps i n the complex cascade leading to Alzheimer's disease and, based on this, to report the current efforts to intervene in these different pathophysiologi cal events in order to prevent progression of Alzheimer's disease. Whereas acetylcholine substitution is currently used in clinical practice, future t herapeutical strategies to combat Alzheimer's disease may include anti-infl ammatory treatments, vaccination against beta amyloid peptide, or treatment with cholesterol-lowering drugs.