Association analysis of peroxisome proliferator-activated receptor gamma polymorphisms and late onset Alzheimer's disease in the Finnish population.

ABSTRACT

Alzheimer's disease (AD), especially late-onset AD (LOAD), is a complex disease. To date, the only established genetic risk factor for LOAD is apolipoprotein E (APOE) epsilon4, which explains partially the risk of the disease and modifies the age of onset. Peroxisome proliferator-activated receptor gamma (PPARgamma) regulates the transcription of BACE1 as well as inflammatory responses in the brain and atherosclerotic risk factors known to be involved also in AD. Based on these findings, the gene encoding PPARgamma can be viewed as an interesting candidate in AD. We examined the effect of the two previously reported variants of PPARgamma polymorphisms, the Pro12Ala and exon 6 C478T, on the risk of LOAD and age of onset in a population-based follow-up sample of aged subjects (125 LOAD patients and 462 non-demented controls). The genetic risk of AD was not significantly associated with the studied polymorphisms, but the PPARgamma Ala12-478T genotype carriers were significantly younger at the onset of dementia than the non-carriers (p = 0.026). These results suggest that the PPARgamma gene may modify the age of onset in LOAD.