Abstract
Alzheimer’s disease (AD) prevalence varies by sex, suggesting that sex chromosomes, sex hormones and/or their signaling could potentially modulate AD risk and progression. Low testosterone levels are reported in men with AD. Further, variation in the androgen receptor (AR) gene has been associated with AD risk and cognitive impairment. We assessed measures of plasma testosterone levels as a biomarker of AD in male participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. Baseline testosterone levels were significantly different between clinical diagnosis groups [cognitively normal controls, mild cognitive impairment (MCI), or AD], with the lowest testosterone levels in men with AD. Lower baseline testosterone levels were associated with higher baseline clinical severity. Change in testosterone levels between baseline and 1-year follow-up varied by diagnosis; MCI had the greatest decreases in testosterone levels between baseline and 1-year follow-up. Despite differences by clinical diagnosis, there was no association between plasma testosterone and CSF biomarkers of AD pathology. We also tested single nucleotide polymorphisms (SNPs) in AR for association with AD risk in a separate cohort from ADNI and found 26 SNPs associated with risk for AD. The top associated SNP is predicted to be an expression quantitative trait locus for AR in multiple tissues, including brain, with the AD-associated risk allele predicted to confer lower AR expression. Our findings suggest a link between the androgen pathway and AD through Aβ/tau independent pathways. These effects may be most pronounced during conversion from MCI to dementia.
Highlights
E Specialty section: This article was submitted to RNeurodegeneration, Alzheimer’s disease (AD) prevalence varies by sex, suggesting that sex chromosomes, sex hormones and/or their signaling could potentially modulate AD risk and progression
We evaluated the relationship between plasma testosterone levels and clinical diagnosis in a subset of men in Alzheimer’s Disease Neuroimaging Initiative (ADNI) (n = 188; Supplementary Table S1)
Baseline testosterone levels were significantly different between cognitively normal controls, mild cognitive impairment (MCI), and AD, with the lowest testosterone levels observed in men with AD (p = 0.02) (Figure 1A)
Summary
This article was submitted to RNeurodegeneration, Alzheimer’s disease (AD) prevalence varies by sex, suggesting that sex chromosomes, sex hormones and/or their signaling could potentially modulate AD risk and progression. We assessed measures of plasma testosterone levels as a biomarker of AD in male participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. Baseline testosterone levels were significantly different between clinical diagnosis groups [cognitively normal controls, mild cognitive impairment (MCI), or AD], with the lowest testosterone levels in men with AD. Lower baseline testosterone levels were associated with higher baseline clinical severity. Despite differences by clinical diagnosis, there was no association between plasma testosterone and CSF biomarkers of AD pathology. Frontiers in Neuroscience for AR in multiple tissues, including brain, with the AD-associated risk allele predicted to Received: 13 March 2018 confer lower AR expression. Accepted: 13 July 2018 and AD through Aβ/tau independent pathways.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
