Examining the influence of sociodemographic and medical factors on plasma p-tau217 performance in diverse communities

ABSTRACT. Alzheimer’s disease (AD) is a public health crisis that disproportionately affects individuals in the Black community. With recent advances in treatment, the need for early identification of AD pathology has never been greater. Early detection allows for early intervention which may be essential to slowing or stopping the

progression of AD prior to widespread, irreversible neuronal loss. Further, early disclosure of increased risk for AD has been shown to motivate positive health behaviors and planning for long-term care. Blood-based biomarkers have been developed to provide a first line screening for the presence of AD pathology. These

biomarkers, such as plasma levels of tau phosphorylated at threonine 217 (p-tau217), have shown great promise as accessible and accurate early indicators of AD pathology, yet these biomarkers have been developed in predominantly White cohorts. Plasma biomarkers are affected by systemic health conditions such

as obesity and chronic kidney disease. These medical conditions disproportionately affect Black adults and may affect the performance of blood-based biomarkers in the Black community. However, the effect of these factors has not yet been quantified in cohorts that are representative of the population and no potential means

of ameliorating any racial differences in plasma p-tau217 performance has yet been investigated. We propose to study the effect of the various sociodemographic and medical factors that disproportionately affect Black adults on plasma p-tau217 levels in local, unique, diverse, and deeply phenotyped cohorts. We will first

quantify the impact of various sociodemographic and medical factors on plasma p-tau217 levels in 3500 individuals (2/3 Black) from the Southern Community Cohort Study. Next, the sociodemographic/medical factors which significantly affected p-tau217 levels will be evaluated as mediators of the association between

p-tau217 and incident dementia to determine if these factors affect the predictive accuracy of this biomarker. Finally, the effect of race on the association between p-tau217 and incident dementia will be investigated in the Vanderbilt Memory and Aging Project and Tennessee Alzheimer’s Project cohorts (estimated n=1300, 325

Black). Should racial differences exist, analyses will be repeated using the plasma p-tau217/amyloid-b42 ratio as predictor to determine if using a ratio increases the predictive accuracy of p-tau217. This proposal will provide excellent training opportunities in the epidemiology of AD, increase my understanding of the causes

and consequences of racial disparities in AD, expand my knowledge and technical expertise for utilizing plasma biomarkers in AD, and provide the essential professional and leadership skills necessary to advance my career as a productive clinician-scientist. These training goals will be accomplished with the aid of an

expert interdisciplinary mentorship team to ensure my success. The skills in AD epidemiology, biostatistics, Medicare claims data analysis, and plasma biomarker analysis gained through this training plan will fuel my future successful independent research program and establish me as a leader in the field of community-based

screening for AD and related dementias.