Improved discrimination of AD patients using beta-amyloid(1-42) and tau levels in CSF
Hulstaert F, Blennow K, Ivanoiu A, Schoonderwaldt HC, Riemenschneider M, De Deyn PP, Bancher C, Cras P et al.. Neurology, 1999-05-01
Topic: Amyloid, tau and blood-test diagnosis
Objective To evaluate CSF levels of beta-amyloid(1-42) (Abeta42) alone and in combination with CSF tau for distinguishing AD from other conditions. Methods At 10 centers in Europe and the United States, 150 CSF samples from AD patients were analyzed and compared with 100 CSF samples from healthy volunteers or patients with disorders not associated with pathologic conditions of the brain (CON), 84 patients with other neurologic disorders (ND), and 79 patients with non-Alzheimer types of dementia (NAD). Sandwich ELISA techniques were used on site for measuring Abeta42 and tau. Results Median levels of Abeta42 in CSF were significantly lower in AD (487 pg/mL) than in CON (849 pg/mL; p = 0.001), ND (643 pg/mL; p = 0.001), and NAD (603 pg/mL; p = 0.001). Discrimination of AD from CON and ND was significantly improved by the combined assessment of Abeta42 and tau. At 85% sensitivity, specificity of the combined test was 86% (95% CI: 81% to 91%) compared with 55% (95% CI: 47% to 62%) for Abeta42 alone and 65% (95% CI: 58% to 72%) for tau. The combined test at 85% sensitivity was 58% (95% CI: 47% to 69%) specific for NAD. The APOE e4 gene load was negatively correlated with Abeta42 levels not only in AD but also in NAD. Conclusions The combined measure of CSF Abeta42 and tau meets the requirements for clinical use in discriminating AD from normal aging and specific neurologic disorders.
Key findings
- Methods At 10 centers in Europe and the United States, 150 CSF samples from AD patients were analyzed and compared with 100 CSF samples from healthy volunteers or patients with disorders not associated with pathologic conditions of the brain (CON), 84 patients with other neurologic disorders (ND), and 79 patients with non-Alzheimer types of dementia (NAD).
- Results Median levels of Abeta42 in CSF were significantly lower in AD (487 pg/mL) than in CON (849 pg/mL; p = 0.001), ND (643 pg/mL; p = 0.001), and NAD (603 pg/mL; p = 0.001).
- Discrimination of AD from CON and ND was significantly improved by the combined assessment of Abeta42 and tau.
- At 85% sensitivity, specificity of the combined test was 86% (95% CI: 81% to 91%) compared with 55% (95% CI: 47% to 62%) for Abeta42 alone and 65% (95% CI: 58% to 72%) for tau.
Why it matters
This study found that measuring both amyloid beta 1-42 and tau in cerebrospinal fluid distinguished Alzheimer's disease from normal aging and other neurologic disorders better than either measure alone. This supports the combined test for clinical diagnosis, but it is a diagnostic study and does not report a treatment, cure, or prevention.
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Study details
- Participants84
- Evidence strengthLow
How this study scored 56/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (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 | 1999 — older than 20 years, still counted |
| Sample size | 1 / 4 | 84 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) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 725 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 25.0 citations a year over 29 year(s) since 1999 |
| Impact for its field and year | 4 / 6 | Cited 16.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 57 other studies in this library |
| Still being cited | 2 / 4 | Cited 31 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Hugo Vanderstichele: h-index 72 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Antwerp: institution h-index 834 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 10331678) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 56 / 100 | — |
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Read the original
Full text: free to read — Unpaywall lists this copy as free to read: the link above (checked 10 Oct 2026).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Hulstaert, F., Blennow, K., Ivanoiu, A., Schoonderwaldt, H. C., Riemenschneider, M., De Deyn, P. P., et al. (1999). Improved discrimination of AD patients using beta-amyloid(1-42) and tau levels in CSF. Neurology. https://doi.org/10.1212/wnl.52.8.1555
Vancouver
Hulstaert F, Blennow K, Ivanoiu A, Schoonderwaldt HC, Riemenschneider M, De Deyn PP, et al. Improved discrimination of AD patients using beta-amyloid(1-42) and tau levels in CSF. Neurology. 1999. doi:10.1212/wnl.52.8.1555. PMID: 10331678.
BibTeX
@article{hulstaert1999-10331678,
author = {Hulstaert, F. and Blennow, K. and Ivanoiu, A. and Schoonderwaldt, H. C. and Riemenschneider, M. and De Deyn, P. P. and Bancher, C. and Cras, P. and others},
title = {{Improved discrimination of AD patients using beta-amyloid(1-42) and tau levels in CSF}},
journal = {Neurology},
year = {1999},
doi = {10.1212/wnl.52.8.1555},
pmid = {10331678},
url = {https://doi.org/10.1212/wnl.52.8.1555}
}
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