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Measurement of phosphorylated tau epitopes in the differential diagnosis of Alzheimer disease: a comparative cerebrospinal fluid study
Hampel H, Buerger K, Zinkowski R, Teipel SJ, Goernitz A, Andreasen N, Sjoegren M, DeBernardis J et al.. Archives of general psychiatry, 2004-01-01
Topic: Amyloid, tau and blood-test diagnosis
Background Abnormal hyperphosphorylation of the microtubule-associated protein tau and its incorporation into neurofibrillary tangles are major hallmarks of the pathogenesis of Alzheimer disease (AD). Different tau phosphoepitopes can be sensitively detected in cerebrospinal fluid (CSF). Objective To compare the diagnostic accuracy of CSF concentrations of tau proteins phosphorylated at 3 pathophysiologically important epitopes (p-tau) to discriminate among patients with AD, nondemented control subjects, and patients with other dementias. Design and setting Cross-sectional, bicenter, memory clinic-based studies. Participants One hundred sixty-one patients with a clinical diagnosis of AD, frontotemporal dementia, dementia with Lewy bodies, or vascular dementia and 45 nondemented controls (N = 206). Main outcome measures Levels of tau protein phosphorylated at threonine 231 (p-tau231), threonine 181 (p-tau181), and serine 199 (p-tau199). The CSF p-tau protein levels were measured using 3 different enzyme-linked immunosorbent assays. Results The mean CSF levels of the studied p-tau proteins were significantly elevated in patients with AD compared with the other groups. Applied as single markers, p-tau231and p-tau181 reached specificity levels greater than 75% between AD and the combined non-AD group when sensitivity was set at 85% or greater. Statistical differences between the assay performances are presented. Particularly, discrimination between AD and dementia with Lewy bodies was maximized using p-tau181at a sensitivity of 94% and a specificity of 64%, and p-tau231 maximized group separation between AD and frontotemporal dementia with a sensitivity of 88% and a specificity of 92%. Combinations of the 3 markers did not add discriminative power compared with the application as single markers. Conclusions The p-tau proteins in CSF come closest to fulfilling the criteria of a biological marker of AD. There is a tendency for p-tau proteins to perform differently in the discrimination of primary dementia disorders from AD.
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APA 7th
Hampel, H., Buerger, K., Zinkowski, R., Teipel, S. J., Goernitz, A., Andreasen, N., et al. (2004). Measurement of phosphorylated tau epitopes in the differential diagnosis of Alzheimer disease: a comparative cerebrospinal fluid study. Archives of general psychiatry. https://doi.org/10.1001/archpsyc.61.1.95
Vancouver
Hampel H, Buerger K, Zinkowski R, Teipel SJ, Goernitz A, Andreasen N, et al. Measurement of phosphorylated tau epitopes in the differential diagnosis of Alzheimer disease: a comparative cerebrospinal fluid study. Archives of general psychiatry. 2004. doi:10.1001/archpsyc.61.1.95. PMID: 14706948.
BibTeX
@article{hampel2004-14706948,
author = {Hampel, H. and Buerger, K. and Zinkowski, R. and Teipel, S. J. and Goernitz, A. and Andreasen, N. and Sjoegren, M. and DeBernardis, J. and others},
title = {{Measurement of phosphorylated tau epitopes in the differential diagnosis of Alzheimer disease: a comparative cerebrospinal fluid study}},
journal = {Archives of general psychiatry},
year = {2004},
doi = {10.1001/archpsyc.61.1.95},
pmid = {14706948},
url = {https://doi.org/10.1001/archpsyc.61.1.95}
}
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Key findings
- Results The mean CSF levels of the studied p-tau proteins were significantly elevated in patients with AD compared with the other groups.
- Combinations of the 3 markers did not add discriminative power compared with the application as single markers.
Why it matters
In 206 memory-clinic patients and controls, this 2004 study found that three forms of phosphorylated tau in spinal fluid (p-tau231, p-tau181 and p-tau199) were on average higher in people clinically diagnosed with Alzheimer's than in non-demented controls or people with frontotemporal, Lewy body or vascular dementia. Used alone, p-tau231 and p-tau181 each ruled out more than 75% of the non-Alzheimer's group when set to detect at least 85% of Alzheimer's cases, and combining all three markers did not improve on a single marker. It is a one-time diagnostic comparison based on clinical diagnoses and does not test any treatment.
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Study details
- Study designcross-sectional
- Participants206
- Evidence strengthLow
How this study scored 58/100
Published in a peer-reviewed journal, and it is a snapshot of people at one point in time. Scored zero for effect reported and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Archives of general psychiatry) |
| Journal's citation record | 4 / 4 | Archives of General Psychiatry: journal h-index 543 (OpenAlex, 2026-10-29) |
| Study design | 4 / 12 | A snapshot of people at one point in time |
| 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 | 2004 — older than 20 years, still counted |
| Sample size | 2 / 4 | 206 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 435 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 18.1 citations a year over 24 year(s) since 2004 |
| Impact for its field and year | 4 / 6 | Cited 13.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 38 other studies in this library |
| Still being cited | 2 / 4 | Cited 37 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Kaj Blennow: h-index 220 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Ludwig-Maximilians-Universität München: institution h-index 1,224 (OpenAlex) |
| Multicenter collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 14706948) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 58 / 100 | — |
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