Behavioural effects of the insertion/deletion polymorphism in Alzheimer's disease depend upon stratification according to -ϵ4 carrier status.

The inherited risk of late-onset Alzheimer's disease (AD) is genetically determined. We aimed to examine associations of genetic variants of and with age at AD onset and with neuropsychiatric symptoms according to each dementia stage. Consecutive outpatients with AD were assessed for demographic features, Clinical Dementia Rating scores, and the 10-item Neuropsychiatric Inventory, and genotyped for rs7412 and rs429358 ( haplotypes, Real-Time Polymerase Chain Reactions), and the insertion/deletion polymorphism (Polymerase Chain Reactions). Combined genetic variants of and were associated with age at dementia onset, and with neuropsychiatric symptoms in each dementia stage (adjusted for sex and age at dementia onset). Over two-thirds of the 238 patients were women, whereas the mean age at dementia onset was 73.82 ± 6.2 years-old. -ϵ4/ϵ4 carriers had earlier dementia onset (<.001). The insertion/deletion polymorphism was in Hardy-Weinberg equilibrium (=.37) but was not associated with age at dementia onset, regardless of -ϵ4 carrier status. The only results that survived corrections for false discovery rates were higher scores of dysphoria for -ϵ4 carriers (=122) who also carried deletion/deletion (=.031). No results survived corrections for false discovery rates for -ϵ4 non-carriers (=116). Though only the -ϵ4/ϵ4 haplotype affected AD onset, effects of the insertion/deletion polymorphism over behavioural features might differ according to -ϵ4 carrier status in genetic associations.