[K23] Examining the influence of sociodemographic and medical factors on plasma p-tau217 performance in at-risk populations
Ente: National Institute on Aging
Scadenza: 2029-04-30
Importo max: 183.789 EUR
Paese: US
Descrizione
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, biostat
Istituzione: VANDERBILT UNIVERSITY MEDICAL CENTER
PI: Corey Bolton
Progetto: 5K23AG084850-03
Settori: National Institute on Aging
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