Genetics of Psychosis in Alzheimer's Disease: A Review

In and of itself, late-onset Alzheimer's disease (AD) can be a devastating illness. However, a sub-group of AD patients develop psychosis as the disease progresses. These patients have an added burden of greater cognitive impairment, higher rates of institutionalization, and higher mortality than AD patients without psychosis. While the etiopathogenesis of psychosis in AD (AD+P) is not known, mounting evidence accrued over the past ten years indicates that AD+P represents a distinct phenotype with a genetic basis. Elucidating the genetic mechanism of AD+P is crucial if better pharmaceutical treatments are to be developed for these patients. The goal of this review is to summarize what is currently known regarding the genetic basis of psychosis in AD. Specific attention is given to familial aggregation and heritability, linkage to chromosomal loci, and associations of candidate genes such as APOE and the monoamine neurotransmitter system.