title: New genes and new insights from old genes: update on Alzheimer disease.
abstract: OBJECTIVE
  This article discusses the current status of knowledge regarding the genetic basis of Alzheimer disease (AD) with a focus on clinically relevant aspects.
  
  
  RESULTS
  The genetic architecture of AD is complex, as it includes multiple susceptibility genes and likely nongenetic factors. Rare but highly penetrant autosomal dominant mutations explain a small minority of the cases but have allowed tremendous advances in understanding disease pathogenesis. The identification of a strong genetic risk factor, APOE, reshaped the field and introduced the notion of genetic risk for AD. More recently, large-scale genome-wide association studies are adding to the picture a number of common variants with very small effect sizes. Large-scale resequencing studies are expected to identify additional risk factors, including rare susceptibility variants and structural variation.
  
  
  CONCLUSIONS
  Genetic assessment is currently of limited utility in clinical practice because of the low frequency (Mendelian mutations) or small effect size (common risk factors) of the currently known susceptibility genes. However, genetic studies are identifying with confidence a number of novel risk genes, and this will further our understanding of disease biology and possibly the identification of therapeutic targets.
authors.affiliation: Easton Center for Alzheimer’s Disease Research at UCLA, 10911 Weyburn Ave, #200, Los Angeles, CA 90095-7226, USA. jringman@mednet.ucla.edu
authors.forename: John M
authors.initials: JM
authors.lastname: Ringman
authors.forename: Giovanni
authors.initials: G
authors.lastname: Coppola
mesh_terms: D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics*; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D053763:Presenilins / Q000235:genetics
chemical_list: D001057:Apolipoproteins E; D053763:Presenilins
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