Genetics of Alzheimer's disease: new evidences for an old hypothesis?

Alzheimer's disease (AD) is the prime cause of dementia and presents a strong genetic predisposition (60–80% of the attributable risk). In addition to APOE, a major recognized genetic determinant of AD, systematic, high-throughput genomic approaches have recently allowed the characterization of four new genetic determinants: CLU, CR1, PICALM and BIN1. Even if the complete picture of AD genetics is still not fully understood, the characterization of these new AD genetic determinants is probably going to strongly modify our perception of the pathophysiological process involved in AD. The new AD genetic landscape suggests that the common and late-onset forms of the disease are associated with a defect in peripheral Aβ peptide clearance, implying that the amyloid cascade hypothesis could be relevant not only in the AD monogenic forms.