Abstract
Alzheimers Dement. 2026 Aug;22(8):e71720. doi: 10.1002/alz.71720.
ABSTRACT
INTRODUCTION: Blood-brain barrier (BBB) dysfunction is an early feature of Alzheimer's disease (AD). Fibrinogen represents a sensitive marker of BBB leakage, but whether it modifies longitudinal tau progression in cognitively unimpaired (CU) individuals remains unknown.
METHODS: CU older adults underwent clinical evaluation and cerebrospinal fluid (CSF) assessment of fibrinogen, Aβ42, total tau (tTau), phosphorylated tau 181 (pTau181), and YKL-40. Linear regression tested baseline associations. Linear mixed-effects models tested whether baseline fibrinogen predicted longitudinal pTau181 change.
RESULTS: Among 169 CU participants with baseline fibrinogen, 87 had longitudinal pTau181 measurements (mean follow-up 2.5-years). Higher fibrinogen was associated with elevated YKL-40 (β = 0.28, 95% confidence interval [CI] [0.11, 0.45]) but not Aβ42, tTau, or pTau181 at baseline. Baseline fibrinogen modified longitudinal pTau181 trajectories (interaction β = 0.11, 95% CI [0.04, 0.19]), with only participants above the median showing significant pTau181 increases (β = 0.13, 95% CI [0.08, 0.18]).
DISCUSSION: CSF fibrinogen associates cross-sectionally with glial inflammation and predicts accelerated tau accumulation in preclinical AD.
PMID:42583778 | DOI:10.1002/alz.71720
UK DRI Authors
