CYP2D6 polymorphisms in Alzheimer’s disease, with and without extrapyramidal signs, showing no apolipoprotein E ε4 effect modification

Abstract Background: Allelic variation at the CYP2D6 gene has been reported to be associated with Parkinsons’ disease (PD) and Lewy body dementia (LBD), but not with Alzheimer’s disease (AD). AD has been associated with apolipoprotein E (apoE) ϵ4 allele loading. Methods: We examined CYP2D6 and apoE polimorphisms in a sample of 259 patients with dementia, 210 of whom had a diagnosis of AD, and 107 healthy controls. Results: We found that the allelic frequency in our AD sample did not vary from that in the controls. The debrisoquine hydroxylase poor metabolize phenotype was not more prevalent among AD cases than among controls in contrast to that reported for PD and LBD. We also found that CYP2D6 status does not modify the risk effect for AD conferred by apoE ϵ4 alleles. Conclusions: These findings provide some support to the notion that, at a genetic level, at least at this locus, AD could be distinct from PD and LBD.