Genomics of Alzheimer's disease: Value of high-throughput genomic technologies to dissect its etiology.
Late-onset Alzheimer's disease (AD), the most common neurodegenerative disorder in western countries, is clinically defined by progressive worsening in cognitive functions along with function and behavioral impairment. This ultimately results in complete incapacity and death. AD is a clinically and pathologically heterogeneous disease, and this is reflected by the numerous genetic findings that point to several diverse molecular mechanisms and pathways. Linkage, genome-wide association and next-generation sequencing studies have led to the identification of more than 20 novel susceptibility loci for AD. While these observations have significantly increased the knowledge of pathogenic mechanisms and potential therapeutic targets, a large part of the genetic component underlying AD is still unexplained. This review will summarize and discuss the major genetic findings and their potential impact on AD diagnosis and prediction of prognosis.
The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA; The Gertrude H. Sergievsky Center, Columbia University, New York, NY, USA; The Department of Neurology, Columbia University, New York, NY, USA.
Giuseppe
G
Tosto
The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA; The Gertrude H. Sergievsky Center, Columbia University, New York, NY, USA; The Department of Neurology, Columbia University, New York, NY, USA; The Dept. of Epidemiology, Columbia University, New York, NY, USA. Electronic address: cr2101@cumc.columbia.edu.
Christiane
C
Reitz
D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics*; D056915:DNA Copy Number Variations; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods*; D023281:Genomics / Q000379:methods*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D009154:Mutation
Alzheimer's disease; Epidemiology of neurodegenerative disorders; Genetics; Genome-wide association study; High-throughput technologies; Rare variants