journal articles
ASSOCIATION OF NEIGHBORHOOD DISADVANTAGE WITH ALZHEIMER\'S DISEASE PATHOLOGY AND THE STABILITY OF BLOOD-BASED BIOMARKER PERFORMANCE
Alison Myoraku, Isabella Hausle, Marta Mila-Aloma, Pamela Thropp, Laura A. Wang, P. Murali Doraiswamy, Duygu Tosun, Alzheimer’s Disease Neuroimaging Initiative
BACKGROUND: Neighborhood-level factors, measured by the Area Deprivation Index (ADI), are linked to comorbidities of Alzheimer's disease and related dementias (ADRD). However, their direct association with AD neuropathology is unclear. The accessibility of blood-based biomarkers (BBMs) like p-tau217 and Aβ42/40 offers a scalable way to investigate these relationships.
OBJECTIVES: To examine the relationship between ADI and levels of key BBMs (p-tau217/Aβ42, p-tau217, and Aβ42/40). We also aimed to assess whether the performance of these BBMs in predicting amyloid PET positivity is consistent across different levels of neighborhood disadvantage.
DESIGN: A cross-sectional analysis using data from an observational cohort study of the Alzheimer’s Disease Neuroimaging Initiative (ADNI).
SETTING: Multicenter observational cohort conducted at 55 sites across the United States.
PARTICIPANTS: The study included 755 ADNI participants with ADI and amyloid PET data. A sub-cohort of 438 participants also had BBM data available.
MEASUREMENTS: National ADI scores were used to stratify participants into least, intermediately, and most disadvantaged groups. Amyloid PET positivity was determined using Centiloid values. Plasma levels of p-tau217, Aβ42, and Aβ40 were measured using Fujirebio assays.
RESULTS: ADI groups differed by sex, ethnoracial background, and MMSE scores. The intermediately disadvantaged group had 1.55 times higher odds of being amyloid PET positive compared to the least disadvantaged group. While this group also showed higher levels of plasma p-tau217/Aβ42 and p-tau217, these differences were no longer significant after accounting for the higher prevalence of amyloid positivity. Critically, the predictive accuracy of all three BBMs for amyloid PET status did not differ across the ADI groups. The p-tau217/Aβ42 ratio performed best, yielding the fewest indeterminate cases in a two-cut-point classification model.
CONCLUSIONS: The diagnostic performance of plasma AD biomarkers is robust and is not compromised by neighborhood-level disadvantage. These findings support the generalizability and equitable clinical utility of biomarkers like p-tau217/Aβ42 for AD diagnosis across diverse socioeconomic settings.
CITATION:
Alison Myoraku ; Isabella Hausle ; Marta Mila-Aloma ; Pamela Thropp ; Laura A. Wang ; P. Murali Doraiswamy ; Duygu Tosun ; Alzheimer’s Disease Neuroimaging Initiative (2025): Association of neighborhood disadvantage with Alzheimer's disease pathology and the stability of blood-based biomarker performance. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100445