Association between atherogenic dyslipidemia and DBS-derived p-tau217 in older adults: evidence from SHARE DBS data

Atherogenic dyslipidemia has been associated with adverse cognitive and dementia-related outcomes, but its relationship with Alzheimer's disease-related blood biomarkers remains unclear.

To examine whether the atherogenic index of plasma (AIP) is associated with dried blood spot (DBS)-derived phosphorylated tau 217 (p-tau217) in older adults from Germany, Sweden, and Denmark.

This cross-sectional analysis included adults aged ≥50 years from Germany, Sweden, and Denmark in the Survey of Health, Ageing and Retirement in Europe DBS biomarker substudy. AIP was calculated as log10(triglycerides/high-density lipoprotein cholesterol). Multivariable linear regression with robust standard errors evaluated standardized natural log-transformed p-tau217, with additional dose-response analyses, comparisons across neurological biomarkers, and sensitivity analyses.

Among 2,676 participants, a 1-SD higher AIP was associated with a 0.074-SD higher ln(p-tau217) (95% CI, 0.034-0.115; p < 0.001), corresponding after back-transformation to a 5.2% higher adjusted geometric mean DBS-derived p-tau217 concentration (95% CI, 2.3-8.1%). The highest versus lowest AIP quartile was associated with higher p-tau217 (β, 0.162; 95% CI, 0.052-0.272; p = 0.004), although estimates across quartiles were not strictly monotonic. Associations were statistically supported for p-tau217 and total tau, but not for GFAP or NfL after FDR correction. Results were robust in sensitivity analyses.

In this cross-sectional analysis, higher AIP, reflecting atherogenic dyslipidemia, was associated with a modestly higher DBS-derived p-tau217 concentration in older adults. The biological and clinical significance of this association remains to be established in longitudinal and multimodal studies.