The effect of the apolipoprotein E gene polymorphisms and haplotypes on behavioural and psychological symptoms in probable Alzheimer's disease.
BACKGROUND
Patients with Alzheimer's disease and dementia commonly suffer from behavioural and psychological symptoms of dementia (BPSD). A genetic component to BPSD development in Alzheimer's disease has been demonstrated. Several studies have investigated whether the exon 4 epsilon2/epsilon3/epsilon4 haplotype of the apolipoprotein E (APOE) gene is associated with BPSD, with variable results.


OBJECTIVE
We investigated the exon 4 polymorphisms and extended this study to include promoter polymorphisms and the resultant haplotypes across the gene.


METHODS
Our large independent cohort of 388 patients with longitudinal measures of BPSD assessed by the Neuropsychiatric Inventory was used to analyse whether any of these variants were associated with the presence of BPSD.


RESULTS
We revealed several significant relationships before correction for multiple testing. The exon 4 haplotype was associated with hallucinations and anxiety, A-491T with irritability, T-427C with agitation/aggression and appetite disturbances, and T-219C with depression. Haplotype analyses of all variants did not reveal any statistically significant findings.


CONCLUSIONS
Our data and a review of previous studies showed a diversity of relationships, suggesting that these findings might be due to chance and so collectively do not support a role for the APOE gene in BPSD.
Pritchard
A L
AL
Molecular Psychiatry Group, Institute of Biomedical Research, University of Birmingham, Birmingham, UK. antonia.pritchard@qimr.edu.au
Harris
J
J
Pritchard
C W
CW
Coates
J
J
Haque
S
S
Holder
R
R
Bentham
P
P
Lendon
C L
CL
D000368:Aged; D000369:Aged, 80 and over; D000374:Aggression; D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics* / Q000523:psychology*; D001007:Anxiety / Q000235:genetics; D053327:Apolipoprotein E4 / Q000235:genetics*; D003863:Depression / Q000235:genetics; D005260:Female; D006212:Hallucinations / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
D053327:Apolipoprotein E4