title: A brief history of Alzheimer's disease gene discovery.
abstract: The rich and colorful history of gene discovery in Alzheimer's disease (AD) over the past three decades is as complex and heterogeneous as the disease, itself. Twin and family studies indicate that genetic factors are estimated to play a role in at least 80% of AD cases. The inheritance of AD exhibits a dichotomous pattern. On one hand, rare mutations inAPP, PSEN1, and PSEN2 are fully penetrant for early-onset (<60 years) familial AD, which represents <5% of AD. On the other hand, common gene polymorphisms, such as the 4 and 2 variants of the APOE gene, influence susceptibility for common (>95%) late-onset AD. These four genes account for 30-50% of the inheritability of AD. Genome-wide association studies have recently led to the identification of additional highly confirmed AD candidate genes. Here, I review the past, present, and future of attempts to elucidate the complex and heterogeneous genetic underpinnings of AD along with some of the unique events that made these discoveries possible.
authors.affiliation: Genetics and Aging Research Unit, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease,Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA. tanzi@helix.mgh.harvard.edu
authors.forename: Rudolph E
authors.initials: RE
authors.lastname: Tanzi
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053764:Presenilin-1 / Q000235:genetics; D053766:Presenilin-2 / Q000235:genetics
chemical_list: D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2