Neurobiology of Disease · Jul 22, 2025

Cross-sectional associations of plasma vitamin D with plasma phosphorylated tau-181 and plasma neurofilament light chain in older adults with memory complaints

By Hooper C, González E, Coley N et al.

BACKGROUND: Lack of vitamin D is associated with cognitive decline and Alzheimer's disease. Therefore, we examined the relationship between plasma 25 hydroxyvitamin D [25(OH)D] and plasma phosphorylated-tau 181 (p-tau 181) and neurofilament light chain (NfL) in older adults with memory complaints. METHODS: This is a cross-sectional analysis of 'Multidomain Alzheimer Preventive Trial' baseline data. Subjects were 519 French community-dwelling adults aged 70⁺ years at risk of dementia with baseline data on plasma 25(OH)D and plasma p-tau 181 and 311 individuals with baseline data on plasma 25(OH)D and plasma NfL. Plasma 25(OH)D, p-tau 181 and NfL were measured using high-sensitivity immune-based assays and associations were explored using adjusted regression analyses. RESULTS: Subjects had a mean (SD) age of 75.2 years (4.3) and 67.6 % were female. The mean (SD) plasma 25(OH)D concentration was 23.5 ng/ml (11.3). The mean (SD) concentrations of plasma p-tau 181 and plasma NfL were 9.9 pg/ml (4.5) and 81.1 pg/ml (34.1) respectively. We did not find significant cross-sectional associations between baseline plasma 25(OH)D and plasma p-tau 181 (Model 3: β-coefficient, 0.0003, 95 % CI: -0.0036, 0.0042, p = 0.879) or plasma 25(OH)D and plasma NfL (Model 3: β-coefficient, -0.0012, 95 % CI: -0.0055, 0.0032, p = 0.599). Age, cognitive status, sex, cardiovascular risk or apolipoprotein ε4 genotype did not modify these non-significant associations. CONCLUSIONS: These findings provide evidence that plasma 25(OH)D is not associated with plasma p-tau 181 or plasma NfL in older adults with heightened dementia risk. Longitudinal replication studies are essential to validate these cross-sectional results.

doi.org/10.1016/j.nbd.2025.107041Open accessPubMed 40706903Biomarkers