title: Rare Variants and Transcriptomics in Alzheimer disease.
abstract: Alzheimer disease (AD) is the most common dementia in the elderly, still without effective treatment. Early-onset AD (EOAD) is caused by mutations in the genesAPP,PSEN1andPSEN2.Genome-wide association studies have identified >20 late-onset AD (LOAD) susceptibility genes with common variants of small risk, with the exception ofAPOE. We review rare susceptibility variants in LOAD with larger effects that have been recently identified in the EOAD geneAPPand the newly discovered AD genesTREM2andPLD3.Human genetic studies now consistently support the amyloid hypothesis of AD for both EOAD and LOAD. Moreover, they identified biological processes that overlap with human transcriptomics studies in AD across different tissues, such as inflammation, cytoskeletal organization, synaptic functions, etc. Transcriptomic profiles of pre-symptomatic AD-associated variant carriers already reflect specific molecular mechanisms reminiscent to those of AD patients. This might provide an avenue for personalized medicine.
authors.affiliation: Department of Human Genetics, John T. Macdonald Foundation, University of Miami, Miller School of Medicine, 1501 NW 10th Avenue (BRB-531), Miami, FL 33136, USA ; John P. Hussman Institute for Human Genomics (HIHG), University of Miami, Miller School of Medicine, 1501 NW 10th Avenue (BRB-531), Miami, FL 33136, USA.
authors.forename: Crystal
authors.initials: C
authors.lastname: Humphries
authors.affiliation: John P. Hussman Institute for Human Genomics (HIHG), University of Miami, Miller School of Medicine, 1501 NW 10th Avenue (BRB-531), Miami, FL 33136, USA.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Kohli
keywords: APP; Alzheimer disease; PLD3; PSEN1; PSEN2; TREM2; dementia; elderly; late-onset Alzheimer disease (LOAD); personalized medicine; transcriptomics