Plasma N-terminal tau fragment levels predict future cognitive decline and neurodegeneration in healthy elderly individuals
Open accessAbstract
The availability of blood-based assays detecting Alzheimer’s disease (AD) pathology should greatly accelerate AD therapeutic development and improve clinical care. This is especially true for markers that capture the risk of decline in pre-symptomatic stages of AD, as this would allow one to focus interventions on participants maximally at risk and at a stage prior to widespread synapse loss and neurodegeneration. Here we quantify plasma concentrations of an N-terminal fragment of tau (NT1) in a large, well-characterized cohort of clinically normal elderly who were followed longitudinally. Plasma NT1 levels at study entry (when all participants were unimpaired) were highly predictive of future cognitive decline, pathological tau accumulation, neurodegeneration, and transition to a diagnosis of MCI/AD. These predictive effects were particularly strong in participants with even modestly elevated brain β-amyloid burden at study entry, suggesting plasma NT1 levels capture very early cognitive, pathologic and neurodegenerative changes along the AD trajectory.
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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 [77]
Plasma tau measurement could be used as a screening test in early-stage clinical trials to enrich trial participation with individuals more likely to have AD pathology.
“Plasma tau measurement could thus be used as a screening test in early-stage clinical trials to enrich trial participation with individuals more likely to have AD pathology (76, 77, 90).”
From All the Tau We Cannot See (2023) · cites this paper as [77]
Plasma tau likely gives information about whether the brain contains neurofibrillary tangles, and plasma tau elevation seems to precede overt clinical symptoms.
“Plasma tau likely does give information about whether the brain contains neurofibrillary tangles, and, like early Braak stages, plasma tau elevation seems to precede overt clinical symptoms (77, 89).”
From All the Tau We Cannot See (2023) · cites this paper as [77]
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- Authors
- Chhatwal, J. P., Schultz, A. P., Dang, Y., Ostaszewski, B., Liu, L., Yang, H.-S., Johnson, K. A., Sperling, R. A., & Selkoe, D. J.
- Affiliations
- Brigham and Women's Hospital (US)
- Harvard University (US)
- Corresponding author
- Sperling, Reisa A.
- Selkoe, Dennis J.
- ORCID
- Venue
- Nature Communications
- Published
- 2020-11-27
- Volume
- 11
- Issue
- 1
- Pages
- 6024-6024
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC7695712
- OpenAlex
- W3108125496
- Cited by
- 60
- References
- 59
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 10 · 2023: 10 · 2022: 14 · 2021: 13
- FWCI
- 6.75
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute on Aging (P01AG036694, R01AG006173, R01AG062667)
- Doris Duke Charitable Foundation (Clinical Scientist Development Award)
- 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 › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, plasma biomarkers, cognitive decline, neurodegeneration, amyloid-beta, mild cognitive impairment, preclinical Alzheimer's disease, healthy older adults, longitudinal cohort
- MeSH terms
- Aged, Alzheimer Disease, Female, Humans, Magnetic Resonance Imaging, Male, Nerve Degeneration, Amyloid beta-Peptides, tau Proteins, Cognitive Dysfunction, Memory, Episodic, Gray Matter
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