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Tau protein in cerebrospinal fluid: a biochemical marker for axonal degeneration in Alzheimer disease?
Blennow K, Wallin A, Agren H, Spenger C, Siegfried J, Vanmechelen E.. Molecular and chemical neuropathology, 1995-12-01
Topic: Brain proteins, microglia and lab models
Cerebrospinal fluid (CSF) biochemical markers for Alzheimer disease (AD) would be of great value to improve the clinical diagnostic accuracy of the disorder. As abnormally phosphorylated forms of the microtubule-associated protein tau have been consistently found in the brains of AD patients, and since tau can be detected in CSF, two assays based on several well-defined monoclonal tau antibodies were used to study these proteins in CSF. One assay detects most normal and abnormal forms of tau (CSF-tau), while the other is highly specific for phosphorylated tau (CSF-PHFtau). A marked increase in CSF-PHFtau was found in AD (2230 +/- 930 pg/mL), as compared with controls (640 +/- 230 pg/mL; p < 0.0001), vascular dementia, VAD (1610 +/- 840 pg/mL; p < 0.05), frontal lobe dementia, FLD (1530 +/- 1000 pg/mL; p < 0.05), Parkinson disease, PD (720 +/- 590 pg/mL; p < 0.0001), and patients with major depression (230 +/- 130 pg/mL; p < 0.0001). Parallel results were obtained for CSF-tau. No less than 35/40 (88%) of AD patients had a CSF-PHFtau value higher than the cutoff level of 1140 pg/mL in controls. The present study demonstrates that elevated tau/PHFtau levels are consistently found in CSF of AD patients. However, a considerable overlap is still present with other forms of dementia, both VAD and FLD. CSF-tau and CSF-PHFtau may therefore be useful as a positive biochemical marker, to discriminate AD from normal aging, PD, and depressive pseudodementia. Further studies are needed to clarify the sensitivity and specificity of these assays, including follow-up studies with neuropathological examinations.
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APA 7th
Blennow, K., Wallin, A., Agren, H., Spenger, C., Siegfried, J., & Vanmechelen, E. (1995). Tau protein in cerebrospinal fluid: a biochemical marker for axonal degeneration in Alzheimer disease? Molecular and chemical neuropathology. https://doi.org/10.1007/bf02815140
Vancouver
Blennow K, Wallin A, Agren H, Spenger C, Siegfried J, Vanmechelen E. Tau protein in cerebrospinal fluid: a biochemical marker for axonal degeneration in Alzheimer disease? Molecular and chemical neuropathology. 1995. doi:10.1007/bf02815140. PMID: 8748926.
BibTeX
@article{blennow1995-8748926,
author = {Blennow, K. and Wallin, A. and Agren, H. and Spenger, C. and Siegfried, J. and Vanmechelen, E.},
title = {{Tau protein in cerebrospinal fluid: a biochemical marker for axonal degeneration in Alzheimer disease?}},
journal = {Molecular and chemical neuropathology},
year = {1995},
doi = {10.1007/bf02815140},
pmid = {8748926},
url = {https://doi.org/10.1007/bf02815140}
}
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Key findings
- A marked increase in CSF-PHFtau was found in AD (2230 +/- 930 pg/mL), as compared with controls (640 +/- 230 pg/mL; p < 0.0001), vascular dementia, VAD (1610 +/- 840 pg/mL; p < 0.05), frontal lobe dementia, FLD (1530 +/- 1000 pg/mL; p < 0.05), Parkinson disease, PD (720 +/- 590 pg/mL; p < 0.0001), and patients with major depression (230 +/- 130 pg/mL; p < 0.0001).
- Parallel results were obtained for CSF-tau.
Why it matters
In this 1995 study, phosphorylated tau in spinal fluid was higher in people with Alzheimer's disease than in controls, people with Parkinson disease and people with major depression, and 35 of 40 Alzheimer's patients were above the cutoff set from the controls. Levels in vascular and frontal lobe dementia were also raised, with "considerable overlap" with Alzheimer's, so the authors suggested the test may help tell Alzheimer's apart from normal aging, Parkinson disease and depression-related memory problems, but not from those other dementias. They said its sensitivity and specificity still needed to be established, including studies with brain examination after death.
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Study details
- Evidence strengthLow
How this study scored 46/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Molecular and chemical neuropathology) |
| Journal's citation record | 0 / 4 | Molecular and Chemical Neuropathology: journal h-index 56 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 1995 — older than 20 years, still counted |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 792 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 24.0 citations a year over 33 year(s) since 1995 |
| Impact for its field and year | 3 / 6 | Cited 4.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 81 other studies in this library |
| Still being cited | 3 / 4 | Cited 77 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Eugeen Vanmechelen: h-index 77 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Bern: institution h-index 977 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 8748926) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 46 / 100 | — |
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