title: Genetics of Psychosis in Alzheimer Disease.
abstract: Psychosis occurs in approximately half of patients with Alzheimer disease (AD with psychosis, AD+P). AD+P patients have more rapid cognitive decline, greater behavioral symptoms, and higher mortality than do AD patients without psychosis. Studies in three independent cohorts have shown that psychosis in AD aggregates in families, with estimated heritability of 29.5 - 60.8%. These findings have motivated studies to investigate and uncover the genes responsible for the development of psychosis, with the ultimate goal of identifying potential biologic mechanisms that may serve as leads to specific therapies. Linkage analyses have implicated loci on chromosomes 2, 6, 7, 8, 15, and 21 with AD+P. Association studies of APOE do not support it as a risk gene for psychosis in AD. No other candidate genes, such as neurodegenerative and monoamine genes, show conclusive evidence of association with AD+P. However, a recent genome-side association study has produced some promising leads, including among them genes that have been associated with schizophrenia. This review summarizes the current knowledge of the genetic basis of AD+P.
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Mary Ann A
authors.initials: MA
authors.lastname: DeMichele-Sweet
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA ; Department of Neurology, University of Pittsburgh, Pittsburgh, PA ; VISN 4 Mental Illness Research, Education and Clinical Center (MIRECC), VA Pittsburgh Healthcare System, Pittsburgh, PA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Sweet
keywords: Alzheimer disease; Association Study; Genome-wide association; Heritability; Linkage Analysis; Psychosis