Myosteatosis, Cognition, and Blood Biomarkers of Alzheimer's Disease in Persons of African Ancestry

Administrative supplement “Sex differences in Alzheimer's Disease blood biomarkers in middle aged persons of African ancestry “ In this administrative supplement, we propose to measure and compare blood levels of Alzheimer's Disease (AD) biomarkers in men and women of African ancestry, aged 45-65, and assess the influence of sex and

adipo-myokines. This proposal extends the goal of the Tobago Brain Study (TBS, RF1AG077474), which is currently focusing on adults aged 65 and older. This proposal is motivated by our recent preliminary results in the TBS cohort aged 65 and older; we find women have worse blood AD biomarkers levels than men independent of age, adiposity, diabetes,

hypertension, or physical activity. We also find that among women (but not men), higher levels of Leptin and IL-6 are associated with worse AD biomarkers' levels, whereas BDNF appears to have a protective effect. Why do older women of African ancestry have greater AD pathology than men and when do these

differences begin? Our hypothesis is that these differences may begin as early as middle-age and are due, at least in part, to mid-life exposure to cardiometabolic diseases and adipo-myokines. If our hypothesis is correct, mid-life intervention on cardiometabolic conditions (and perhaps also on selected cytokines) could reduce

amyloid disparities in this high-risk population. We propose to measure blood AD biomarkers and inflammatory adipo-myokines in 190 men and women of African ancestry in Tobago, aged 45-64-years, whose samples are stored at the University of Pittsburgh. This proposal is time-sensitive; the results will inform a new grant to add recruitment of middle-aged women and

men while the TBS is still actively recruiting, thus maximizing our chances of success as well as NIA existing investment in resources and infrastructure. This proposal has high potential impact: it will increase the likelihood for the parent TBS to exert a sustained, powerful influence on the research field of AD risk in persons

of African ancestry, especially women in middle-age, a critical window of time for exposure to AD risk factors.