Genetic Variation in the Androgen Receptor and Measures of Plasma Testosterone Levels Suggest Androgen Dysfunction in Alzheimer's Disease.

摘要: Alzheimer's disease (AD) prevalence varies by sex, suggesting that sex chromosomes, hormones and/or their signaling could potentially modulate AD risk and progression. Low testosterone levels are reported in men with AD. Further, variation the androgen receptor (AR) gene has been associated cognitive impairment. We assessed measures of plasma as a biomarker male participants from Disease Neuroimaging Initiative (ADNI) cohort. Baseline were significantly different between clinical diagnosis groups [cognitively normal controls, mild impairment (MCI), or AD], lowest Lower baseline higher severity. Change 1-year follow-up varied diagnosis; MCI had greatest decreases follow-up. Despite differences diagnosis, there was no association CSF biomarkers pathology. also tested single nucleotide polymorphisms (SNPs) AR for separate cohort ADNI found 26 SNPs The top SNP is predicted to be an expression quantitative trait locus multiple tissues, including brain, AD-associated allele confer lower expression. Our findings suggest link pathway through Aβ/tau independent pathways. These effects may most pronounced during conversion dementia.