Review: Tau in biofluids – relation to pathology, imaging and clinical features
Open accessAbstract
Tau is a microtubule‐binding protein that is important for the stability of neuronal axons. It is normally expressed within neurons and is also secreted into the brain interstitial fluid that communicates freely with cerebrospinal fluid (CSF) and, in a more restricted manner, blood via the glymphatic clearance system of the brain. In Alzheimer's disease (AD), neuroaxonal degeneration results in increased release of tau from neurons. Furthermore, tau is truncated and phosphorylated, which leads to aggregation of tau in neurofibrillary tangles of the proximal axoplasm. Neuroaxonal degeneration and tangle formation are reflected by increased concentrations of total tau (T‐tau, measured using assays that detect most forms of tau) and phospho‐tau (P‐tau, measured using assays with antibodies specific to phosphorylated forms of tau). In AD CSF, both T‐tau and P‐tau concentrations are increased. In stroke and other CNS disorders with neuroaxonal injury but without tangles, T‐tau is selectively increased, whereas P‐tau concentration often stays normal. In tauopathies (diseases with both neurodegeneration and neurofibrillary tangles) other than AD, CSF T‐tau and P‐tau concentrations are typically unaltered, which is a puzzling result that warrants further investigation. In the current review, I discuss the association of T‐tau and P‐tau concentrations in body fluids with neuropathological changes, imaging findings and clinical features in AD and other CNS diseases.
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In acute conditions like traumatic brain injury and hypoxic brain injury, plasma total tau measured by the same assay increases quickly, with an apparent half-life near 10 hours, while CSF total tau has a half-life near 20 days.
“In acute conditions, like traumatic brain injury and hypoxic brain injury, plasma t-tau concentrations measured using the same technology as the one employed here increase rapidly and show an apparent half-life of around 10 hours, 41 which contrasts with the half-life of CSF t-tau, which is about 20 days.42”
From Plasma Tau and Neurofilament Light in Frontotemporal Lobar Degeneration and Alzheimer Disease (2021) · cites this paper as [41]
The Plasma tau section reports rapid increases after hypoxic brain injury and concussion, and says tau’s half-life appears to be measured in hours in plasma versus weeks in CSF. It does not give the specific estimates of approximately 10 hours and 20 days. The section identifies Simoa as a blood-tau measurement platform, but does not establish that it is the same assay used by the citing authors. (LLM, conf=0.87)
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- Authors
- Zetterberg, H.
- Affiliations
- Sahlgrenska University Hospital (SE)
- Corresponding author
- Zetterberg, H.
- ORCID
- Zetterberg, H.
- Venue
- Neuropathology and Applied Neurobiology
- Publisher
- Wiley
- Published
- 2017-04
- Volume
- 43
- Issue
- 3
- Pages
- 194-199
- ISSN
- 0305-1846 (ISSN-L)
- 1365-2990
- OpenAlex
- W2571295372
- Cited by
- 157
- References
- 40
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 18 · 2023: 14 · 2022: 26 · 2021: 18 · 2020: 16 · 2019: 21 · 2018: 20 · 2017: 7
- FWCI
- 2.15
- Type
- journal article
- Language
- en
- Open access
- green
- discovery.ucl.ac.uk
- Locations
- Neuropathology and Applied Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Vetenskapsrådet
- H2020 European Research Council
- Wolfson Foundation
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Keywords
- tau protein, cerebrospinal fluid biomarkers, total tau, phosphorylated tau, Alzheimer's disease, tauopathy, neuroaxonal degeneration, neurofibrillary tangles, glymphatic system, stroke, brain interstitial fluid, neuroimaging, clinical features
- MeSH terms
- Central Nervous System Diseases, Humans, tau Proteins
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