Christos Panagiotis Lisgaras, Tovia Jacobs, Luisa Figueredo, Elizabeth Pirraglia, Caleb H Radtke, Jonah N Keller, Nikolaos Karvelas, Jennifer Bernal, Joaquin Ruiz, Henrik Zetterberg, Lidia Glodzik, Mony J de Leon, Laura Beth McIntire, Allal Boutajangout, Thomas Wisniewski, Jaime Ramos-Cejudo, Daniel Alcolea, Sandra Giménez, Juan Fortea, Katerina Akassoglou, Fanny M Elahi, Ricardo S Osorio
EEG is a promising, non-invasive, and cost-effective tool for early AD detection in appropriate clinical and research settings. The integration of advanced signal processing with intelligent algorithms can significantly improves diagnostic precision, though clinical translation requires standardized protocols and validation on larger, diverse cohorts.
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.