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Plasma β-Amyloid, Total-Tau, and Neurofilament Light Chain Levels and the Risk of Stroke: A Prospective
Alis Heshmatollah1, Lana Fani1, Peter J Koudstaal1
1From the Departments of Epidemiology (A.H., L.F., M.G., M.A.I., M.K.I.) and Neurology (A.H., P.J.K., M.K.I.), Erasmus MC University Medical Center, Rotterdam, the Netherlands.
Background And Objectives:
To unravel whether Alzheimer disease-related pathology or neurodegeneration plays a role in stroke etiology, we determined the effect of plasma levels β-amyloid (Aβ), total-tau, and neurofilament light chain (NfL) on risk of stroke and its subtypes.
Methods:
Between 2002 and 2005, we measured plasma Aβ40, Aβ42, total-tau, and NfL in 4,661 stroke-free participants from the population-based Rotterdam Study. We used Cox proportional-hazards models to determine the association between these markers with incident stroke for the entire cohort, per stroke subtype, and by median age, sex, APOE ε4 carriership, and education.
Results:
After a mean follow-up of 10.8 ± 3.3 years, 379 participants had a first-ever stroke. Log2 total-tau at baseline showed a nonlinear association with risk of any stroke and ischemic stroke: compared to the first (lowest) quartile, the adjusted hazard ratio (HR) for the highest quartile total-tau was 1.68 (95% CI 1.18-2.40) for any stroke. Log2 NfL was associated with an increased risk of any stroke (HR per 1-SD increase 1.27, 95% CI 1.12-1.44), ischemic stroke, and hemorrhagic stroke (HR 1.56, 95% CI 1.14-2.12). Log2 Aβ40, Aβ42, and Aβ42/40 ratio levels were not associated with stroke risk.
Discussion:
Participants with higher total-tau and NfL at baseline had a higher risk of stroke and several stroke subtypes. These findings support the role of markers of neurodegeneration in the etiology of stroke.
Classification Of Evidence:
This study provides Class II evidence that higher plasma levels of total-tau and NfL are associated with an increased risk of subsequent stroke.
