Plasma neurofilament light and phosphorylated tau 181 as biomarkers of Alzheimer’s disease pathology and clinical disease progression
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Abstract
Background: To assess the performance of plasma neurofilament light (NfL) and phosphorylated tau 181 (p-tau181) to inform about cerebral Alzheimer’s disease (AD) pathology and predict clinical progression in a memory clinic setting. Methods: Plasma NfL and p-tau181, along with established cerebrospinal fluid (CSF) biomarkers of AD pathology, were measured in participants with normal cognition (CN) and memory clinic patients with cognitive impairment (mild cognitive impairment and dementia, CI). Clinical and neuropsychological assessments were performed at inclusion and follow-up visits at 18 and 36 months. Multivariate analysis assessed associations of plasma NfL and p-tau181 levels with AD, single CSF biomarkers, hippocampal volume, and clinical measures of disease progression. Results: Plasma NfL levels were higher in CN participants with an AD CSF profile (defined by a CSF p-tau181/Aβ 1–42 > 0.0779) as compared with CN non-AD, while p-tau181 plasma levels were higher in CI patients with AD. Plasma NfL levels correlated with CSF tau and p-tau181 in CN, and with CSF tau in CI patients. Plasma p-tau181 correlated with CSF p-tau181 in CN and with CSF tau, p-tau181, Aβ 1–42 , and Aβ 1–42 /Aβ 1–40 in CI participants. Compared with a reference model, adding plasma p-tau181 improved the prediction of AD in CI patients while adding NfL did not. Adding p-tau181, but not NfL levels, to a reference model improved prediction of cognitive decline in CI participants. Conclusion: Plasma NfL indicates neurodegeneration while plasma p-tau181 levels can serve as a biomarker of cerebral AD pathology and cognitive decline. Their predictive performance depends on the presence of cognitive impairment.
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Plasma tau has emerged as a marker of neuronal distress and appears in several neurodegenerative diseases, including preclinical AD.
“Like NfL (neurofilament light chain), plasma tau has emerged as a marker of neuronal distress. It appears in several different neurodegenerative diseases, including importantly even preclinical AD patients (76–85).”
From All the Tau We Cannot See (2023) · cites this paper as [78]
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- Authors
- Clark, C., Lewczuk, P., Kornhuber, J., Richiardi, J., Maréchal, B., Karikari, T. K., Blennow, K., Zetterberg, H., & Popp, J.
- Affiliations
- University of Zurich (CH)
- Medical University of Białystok (PL)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Centre Hospitalier Universitaire Vaudois (CH)
- Sahlgrenska University Hospital (SE)
- Corresponding author
- Clark, Christopher
- ORCID
- Venue
- Alzheimer's Research & Therapy
- Published
- 2021-03-25
- Volume
- 13
- Issue
- 1
- Pages
- 65-65
- ISSN
- 1758-9193 (ISSN-L)
- PMC
- PMC7995778
- OpenAlex
- W3118616512
- Cited by
- 88
- References
- 31
- Citations by year
- 2026: 8 · 2025: 16 · 2024: 17 · 2023: 20 · 2022: 22 · 2021: 5
- FWCI
- 11.47
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Alzheimer s Research & Therapy (publishedVersion, cc-by)
- Research Square (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- SERVAL (Université de Lausanne) (publishedVersion, cc-by)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by)
- IRIS (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- UCL Discovery (University College London) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (320030_141179)
- Stiftung Synapsis - Alzheimer Forschung Schweiz AFS (2017-PI01)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Keywords
- Alzheimer's disease, plasma neurofilament light, phosphorylated tau 181, plasma biomarkers, cerebrospinal fluid biomarkers, mild cognitive impairment, dementia, cognitive decline, disease progression, neurodegeneration, amyloid-beta, hippocampal volume, CSF tau
- MeSH terms
- Alzheimer Disease, Humans, Intermediate Filaments, Biomarkers, Amyloid beta-Peptides, tau Proteins, Disease Progression, Cognitive Dysfunction
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