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Abstract
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.
Glossary
- Aβ=
- β-amyloid;
- AD=
- Alzheimer disease;
- BMI=
- body mass index;
- CAA=
- cerebral amyloid angiopathy;
- HDL=
- high-density lipoprotein;
- HR=
- hazard ratio;
- ICD-10=
- International Classification of Diseases, 10th revision;
- NfL=
- neurofilament light chain;
- Simoa=
- single-molecule array;
- STROBE=
- Strengthening the Reporting of Observational Studies
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
↵* These authors contributed equally to this work.
See page e1794
Class of Evidence: NPub.org/coe
- Received April 7, 2021.
- Accepted in final form January 3, 2022.
- © 2022 American Academy of Neurology
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