Association of plasma p-tau217 levels with cerebral small vessel disease burden: Cross-sectional insights from the Hefei Aging Study

BACKGROUND: Phosphorylated tau (p-tau217) is a well-established and recognized biomarker for Alzheimer's disease (AD), however, its relationship with cerebral small vessel disease (CSVD) remains inadequately explored. This study examines the association between plasma p-tau217 levels and CSVD burden within a community-based cohort. METHODS: We conducted a cross-sectional analysis of data from 515 participants aged years and older enrolled in the Hefei Aging Study (HAS). CSVD burden was quantified using magnetic resonance imaging (MRI) markers, including white matter hyperintensities (WMH), lacunar infarcts, cerebral microbleeds (CMBs), and enlarged perivascular spaces (EPVS). Associations were evaluated using logistic regression and generalized linear models, adjusting for relevant covariates. RESULTS: Individuals with CSVD (score ≥1, n = 145) had significantly higher median p-tau217 levels compared to those without CSVD (0.245 vs. 0.227 pg/mL, p = 0.010). Elevated p-tau217 was independently associated with WMH (odds ratio [OR] =1.462, p = 0.006) and CMBs (OR =1.290, p = 0.033) after adjusting for covariates. Stratified analyses indicated stronger associations in APOE ε4-negative individuals (OR=1.244, p = 0.027). A linear relationship was observed between log-transformed p-tau217 and CSVD burden (β =0.113, p < 0.001), although the effect sizes were modest (adjusted R² =0.025). CONCLUSION: Plasma p-tau217 levels are associated with CSVD burden, particularly WMH and CMBs, suggesting a role for tau pathology in vascular injury. The APOE ε4 genotype appears to modulate this relationship, highlighting distinct pathways in amyloid- and tau-mediated vascular damage.