APOE AND CYP2D6 POLYMORPHISM WITH AND WITHOUT PARKINSONISM-DEMENTIA COMPLEX IN THE PEOPLE OF CHAMORRO, GUAM

Parkinsonism-dementia complex (PDC), a neurodegenerative disorder in t he Chamorro, Guam population, has been epidemiologically ascribed to t he ingestion of the neurotoxin cycasin. This disease is characterized neuropathologically by the presence of abundant neurofibrillary tangle s (NFTs). We analyzed a genetic risk factor of Alzheimer's disease (AD ), apolipoprotein E, hypothesized to be linked to NFT formation, and a genetic risk factor of Parkinson's disease (PD), CYP2D6 mutation, lin ked to slower metabolism of exogenous toxins, in Chamorro, Guam indivi duals with and without PDC. The representation of the G-to-C mutation in exon 9 of the CYP2D6 gene was higher in Chamorro and Filipino than in Caucasian individuals, but this mutant allele had similar high freq uencies in both PDC patients and healthy Chamorro individuals. We foun d no alleles of these genes associated with AD or PD to be overreprese nted among those with PDC.