HAI Book 2025 - Flipbook - Page 199
Arnold, Steven
40
P-TAU217, GFAP, and NFL plasma biomarker associations with
demographic, medical and neurocognitive features from middle-aged
through older adulthood
Steven Arnold1, Pia Kivisakk1, Hadia Fatima1, Jennifer Gentsch2, Carlos Cruchaga2, Chao-Yi
Wu1, Hiroko Dodge1, Beau Ances1,2, David Salat1
1
Massachusetts General Hospital, Harvard Medical School, Boston, MA, US
Washington University in St. Louis, Saint Louis, MO, US
2
The Adult Aging Brain Connectome (AABC) study follows healthy adults, ages 36-100+ from diverse backgrounds at
four sites across the U.S.A., evaluating demographic, genetic, molecular, neurocognitive and anatomic/functional
brain imaging characteristics. Its principal goals are to identify and understand risk and resilience factors for
cognitive brain aging across the mature adult lifespan. Here we present current baseline data on phospho-tau 217
(pTau217), glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) plasma biomarkers in the AABC and
their associations with age, race and ethnicity, cardiovascular-metabolic health factors and global indices of
cognition in different stages of adulthood.
The sample for analysis consisted of 652 individuals with a mean age 65.9 (s.d.15.4, range 36-100+), roughly equally
distributed in three age categories - Younger Mature (36-55), Older (56-75), and Oldest (76+). 54.1% were Female
and 45.9% Male. Racial identities included Asian 4.9%, Black/African-American 15.2%, Multi/Other 6.3%, and
White 73.6%. 11.5% identified as Hispanic/Latino.
In univariate analyses, age was strongly correlated with all three biomarkers across the entire sample and within
each age category, most highly in the Older (56-75) category. Across the age spectrum, women had lower levels of
pTau217, higher GFAP, and no differences in NfL compared to men. There were significant differences for all
biomarkers by race and ethnicity with higher values in Whites and Non-Hispanics overall and within each age
category. In linear regression models adjusted for age, sex, race and ethnicity, differing indices of
cardiovascular-metabolic factors were significantly associated with pTau217, GFAP and NfL. Finally, in fully
adjusted models, higher pTau217 and NfL were significantly associated with lower cognitive performance overall,
and especially in the Older and Oldest categories.
These data on robust blood-based biomarkers of AD and neurodegeneration identify early changes in AD
biomarkers and their associations with cardiovascular-metabolic factors and cognition across the mature adult
lifespan.
Keywords: p-tau, gfap, nfl, lifespan, cardiovascular
HAI2025 - 199
