Cross-Sectional and Longitudinal Associations of Neighborhood Disadvantage With Fluid Biomarkers of Neuroinflammation and Neurodegeneration

Neurology. 2025 Jul 22;105(2):e213770. doi: 10.1212/WNL.0000000000213770. Epub 2025 Jun 25.

ABSTRACT

BACKGROUND AND OBJECTIVES: Living in a socioeconomically disadvantaged neighborhood has an adverse impact on health outcomes, including increased risk of Alzheimer disease (AD). The biological mechanisms underlying this risk are poorly understood. We sought to examine how neighborhood disadvantage relates to core AD pathology, neurodegeneration, and inflammatory biomarkers in community-dwelling older adults cross-sectionally and over time.

METHODS: Participants included older adults from the Vanderbilt Memory and Aging Project who underwent fasting blood and CSF acquisition serially over a 9-year follow-up period (mean follow-up = 6.4 years [blood] and 4.0 years [CSF]). Area Deprivation Index (ADI), representing neighborhood disadvantage, was quantified at baseline using 17 components (e.g., housing, income, education, and household characteristics), with higher values indicating greater disadvantage. Ordinary least-squares regressions cross-sectionally related ADI to plasma and CSF inflammatory biomarkers adjusting for age, sex, race/ethnicity, education, modified Framingham Stroke Risk Profile score, APOE ε4 status, and cognitive status. Linear mixed-effects regression models related ADI to longitudinal biomarkers with identical covariates plus follow-up time. Outcomes included CSF chitinase-3-like protein 1 (YKL-40), CSF soluble-triggering receptor expressed on myeloid cells 2, CSF amyloid-β₄₂ (Aβ₄₂), CSF Aβ₄₀/Aβ₄₂ ratio, CSF tau, CSF phosphorylated tau (ptau), plasma high-sensitivity C-reactive protein (CRP), and plasma and CSF neurofilament light chain.

RESULTS: Participants (n = 334; 73 ± 8 years old, 59% male, 86% White, non-Hispanic) on average were from relatively less disadvantaged neighborhoods (ADI national decile = 33 ± 25, range = 1-98). Greater neighborhood disadvantage at study entry was cross-sectionally associated with elevated CSF YKL-40 (β = 0.7, p = 0.003) and tau (β = 1.8, p = 0.04) after excluding outliers. Greater neighborhood disadvantage at study entry related to faster longitudinal increases in plasma CRP (β = 0.005, p = 0.03).

DISCUSSION: Greater neighborhood disadvantage was associated with elevated inflammatory and AD CSF biomarkers cross-sectionally and longitudinal increases in a nonspecific inflammatory blood biomarker. Findings suggest that neighborhood disadvantage confers risk of systemic inflammation and AD pathology, providing a possible sociobiological mechanism underlying health disparities in aging adults; however, results were limited by use of ADI at study entry.

PMID:40561381 | DOI:10.1212/WNL.0000000000213770