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The 14-3-3 brain protein in cerebrospinal fluid as a marker for transmissible spongiform encephalopathies
Hsich G, Kenney K, Gibbs CJ, Lee KH, Harrington MG.. The New England journal of medicine, 1996-09-01
Topic: Brain proteins, microglia and lab models
Background There is no practical and reliable premortem test for Creutzfeldt-Jakob disease and the related transmissible spongiform encephalopathies. Two proteins, designated 130 and 131, which have been detected in low concentrations in cerebrospinal fluid from patients with Creutzfeldt-Jakob disease, appear to be sensitive and specific markers for the disease. Attempts to identify these proteins, however, have been unsuccessful. We hypothesized that they may be present in the normal brain. Methods We detected proteins 130 and 131 in normal human brain, partially sequenced their amino acids, and found that they matched the brain protein known as 14-3-3. We then developed a simple, rapid immunoassay for this protein and tested it in cerebrospinal fluid samples from 71 humans and 30 animals with spongiform encephalopathies and in control samples from 186 humans and 94 animals. Results The immunoassay detected the 14-3-3 protein in cerebrospinal fluid from 68 of the 71 patients with Creutzfeldt-Jakob disease (96 percent, 95 percent confidence interval, 92 to 99 percent). Among 94 patients with other dementias, the specificity was 96 percent. If one excludes the three patients with dementia who had strokes within one month before testing, the specificity was 99 percent. The test was positive in 12 of 24 patients with viral encephalitis. In animals the sensitivity of the assay was 87 percent and the specificity was 99 percent. Conclusion In patients with dementia, a positive immunoassay for the 14-3-3 brain protein in cerebrospinal fluid strongly supports a diagnosis of Creutzfeldt-Jakob disease. This finding, however, does not support the use of the test in patients without clinically evident dementia.
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APA 7th
Hsich, G., Kenney, K., Gibbs, C. J., Lee, K. H., & Harrington, M. G. (1996). The 14-3-3 brain protein in cerebrospinal fluid as a marker for transmissible spongiform encephalopathies. The New England journal of medicine. https://doi.org/10.1056/nejm199609263351303
Vancouver
Hsich G, Kenney K, Gibbs CJ, Lee KH, Harrington MG. The 14-3-3 brain protein in cerebrospinal fluid as a marker for transmissible spongiform encephalopathies. The New England journal of medicine. 1996. doi:10.1056/nejm199609263351303. PMID: 8782499.
BibTeX
@article{hsich1996-8782499,
author = {Hsich, G. and Kenney, K. and Gibbs, C. J. and Lee, K. H. and Harrington, M. G.},
title = {{The 14-3-3 brain protein in cerebrospinal fluid as a marker for transmissible spongiform encephalopathies}},
journal = {The New England journal of medicine},
year = {1996},
doi = {10.1056/nejm199609263351303},
pmid = {8782499},
url = {https://doi.org/10.1056/nejm199609263351303}
}
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Key findings
- Results The immunoassay detected the 14-3-3 protein in cerebrospinal fluid from 68 of the 71 patients with Creutzfeldt-Jakob disease (96 percent, 95 percent confidence interval, 92 to 99 percent).
Why it matters
This study describes a cerebrospinal fluid test for the 14-3-3 protein that detected Creutzfeldt-Jakob disease in 68 of 71 patients. It concerns diagnosis of transmissible spongiform encephalopathies, not the treatment, cure or prevention of Alzheimer's disease.
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Study details
- Participants71
- Evidence strengthLow
How this study scored 56/100
Published in a top-tier journal. Scored zero for study design, effect reported and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (The New England journal of medicine) |
| Journal's citation record | 4 / 4 | New England Journal of Medicine: journal h-index 1,505 (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 | 1996 — older than 20 years, still counted |
| Sample size | 1 / 4 | 71 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 661 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 20.7 citations a year over 32 year(s) since 1996 |
| Impact for its field and year | 4 / 6 | Cited 14.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 8 other studies in this library |
| Still being cited | 2 / 4 | Cited 22 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Michael G. Harrington: h-index 48 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | National Institutes of Health: institution h-index 2,723 (OpenAlex) |
| Multicenter collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 8782499) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 56 / 100 | — |
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