The pursuit of susceptibility genes for Alzheimer's disease: progress and prospects

The recent discoveries in genome-wide association studies (GWAS) of novel susceptibility loci (CLU, CR1 and PICALM) for Alzheimer''s disease (AD) have elicited considerable interest in the AD community. But what are the implications of these purely epidemiological findings for our understanding of disease etiology and patient care? In this review, we attempt to place these findings in the context of current and future AD genetics research. CLU, CR1 and PICALM support existing hypotheses about the amyloid, lipid, chaperone and chronic inflammatory pathways in AD pathogenesis. We discuss how these and future findings can be translated into efforts to ameliorate patient care by genetic profiling for risk prediction and pharmacogenetics and by guiding drug development. [Copyright &y& Elsevier]