Plasma β-Amyloid, Total-Tau, and Neurofilament Light Chain Levels and the Risk of Stroke: A Prospective Population-Based Study

Alis Heshmatollah; Lana Fani; Peter J. Koudstaal; Mohsen Ghanbari; M. Arfan Ikram; M. Kamran Ikram

doi:10.1212/WNL.0000000000200004

Plasma β-Amyloid, Total-Tau, and Neurofilament Light Chain Levels and the Risk of Stroke: A Prospective Population-Based Study

Alis Heshmatollah^*, Lana Fani, Peter J. Koudstaal, Mohsen Ghanbari, M. Arfan Ikram, M. Kamran Ikram

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

16 Citations (Scopus)

Abstract

Background and ObjectivesTo 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.MethodsBetween 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.ResultsAfter 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.DiscussionParticipants 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 EvidenceThis study provides Class II evidence that higher plasma levels of total-tau and NfL are associated with an increased risk of subsequent stroke.

Original language	English
Pages (from-to)	E1729-E1737
Journal	Neurology
Volume	98
Issue number	17
DOIs	https://doi.org/10.1212/WNL.0000000000200004
Publication status	Published - 26 Apr 2022

Bibliographical note

Funding Information:
The Rotterdam Study is supported by the Erasmus MC University Medical Center and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research; the Netherlands Organization for Health Research and Development; the Research Institute for Diseases in the Elderly; the Netherlands Genomics Initiative); the Ministry of Education, Culture and Science; the Ministry of Health, Welfare and Sports; the European Commission (DG XII); and the Municipality of Rotterdam.

Publisher Copyright:
© American Academy of Neurology.

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10.1212/WNL.0000000000200004

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@article{525c201755584bd4acbda337826d3a68,

title = "Plasma β-Amyloid, Total-Tau, and Neurofilament Light Chain Levels and the Risk of Stroke: A Prospective Population-Based Study",

abstract = "Background and ObjectivesTo 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.MethodsBetween 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.ResultsAfter 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.DiscussionParticipants 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 EvidenceThis study provides Class II evidence that higher plasma levels of total-tau and NfL are associated with an increased risk of subsequent stroke.",

author = "Alis Heshmatollah and Lana Fani and Koudstaal, {Peter J.} and Mohsen Ghanbari and Ikram, {M. Arfan} and Ikram, {M. Kamran}",

note = "Funding Information: The Rotterdam Study is supported by the Erasmus MC University Medical Center and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research; the Netherlands Organization for Health Research and Development; the Research Institute for Diseases in the Elderly; the Netherlands Genomics Initiative); the Ministry of Education, Culture and Science; the Ministry of Health, Welfare and Sports; the European Commission (DG XII); and the Municipality of Rotterdam. Publisher Copyright: {\textcopyright} American Academy of Neurology.",

year = "2022",

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day = "26",

doi = "10.1212/WNL.0000000000200004",

language = "English",

volume = "98",

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T1 - Plasma β-Amyloid, Total-Tau, and Neurofilament Light Chain Levels and the Risk of Stroke

T2 - A Prospective Population-Based Study

AU - Heshmatollah, Alis

AU - Fani, Lana

AU - Koudstaal, Peter J.

AU - Ghanbari, Mohsen

AU - Ikram, M. Arfan

AU - Ikram, M. Kamran

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PY - 2022/4/26

Y1 - 2022/4/26

N2 - Background and ObjectivesTo 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.MethodsBetween 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.ResultsAfter 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.DiscussionParticipants 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 EvidenceThis study provides Class II evidence that higher plasma levels of total-tau and NfL are associated with an increased risk of subsequent stroke.

AB - Background and ObjectivesTo 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.MethodsBetween 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.ResultsAfter 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.DiscussionParticipants 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 EvidenceThis study provides Class II evidence that higher plasma levels of total-tau and NfL are associated with an increased risk of subsequent stroke.

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Plasma β-Amyloid, Total-Tau, and Neurofilament Light Chain Levels and the Risk of Stroke: A Prospective Population-Based Study

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