Missense substitutions associated with behavioural disturbances in Alzheimer's disease (AD)

Behavioural and psychological symptoms in dementia, or BPSD, occur in the majority of Alzheimer's disease (AD) patients. They are associated with considerable patient morbidity and greater care-giver stress. There is some evidence suggesting that BPSD have a genetic component and a large number of studies have examined the association of candidate genes with these symptoms. This review provides a comprehensive summary of all the published studies investigating the association of candidate gene missense substitutions with BPSD. Missense substitutions could potentially alter protein function or render the protein non-functional, resulting in phenotypic consequences. More than 80 studies investigating the association of 8 missense substitutions in 7 genes with BPSD were identified. However, results of these studies are contradictory and do not provide firm support for these associations. Larger studies and more systematic approaches will delineate the association of missense substitutions with behavioural symptoms in AD.

► Behavioural and psychological symptoms in dementia (BPSD) may have a genetic basis.
► Most studies on the genetics of BPSD have implicated missense substitutions.
► 8 missense substitutions in 7 genes have been implicated in BPSD.
► These are APOE, 5HT2C, DRD2, DRD3, COMT, BDNF and NRG1.
► Many interesting associations have been reported, but studies are contradictory.