The brain injury biomarker VLP-1 is increased in the cerebrospinal fluid of Alzheimer disease patients
Lee JM, Blennow K, Andreasen N, Laterza O, Modur V, Olander J, Gao F, Ohlendorf M et al.. Clinical chemistry, 2008-08-14
Topic: Amyloid, tau and blood-test diagnosis
Background Definitive diagnosis of Alzheimer disease (AD) can be made only by histopathological examination of brain tissue, prompting the search for premortem disease biomarkers. We sought to determine if the novel brain injury biomarker, visinin-like protein 1 (VLP-1), is altered in the CSF of AD patients compared with controls, and to compare its values to the other well-studied CSF biomarkers 42-amino acid amyloid-beta peptide (Abeta(1-42)), total Tau (tTau), and hyperphosphorylated Tau (pTau). Methods Using ELISA, we measured concentrations of Abeta(1-42), tTau, pTau, and VLP-1 in CSF samples from 33 AD patients and 24 controls. We compared the diagnostic performance of these biomarkers using ROC curves. Results CSF VLP-1 concentrations were significantly higher in AD patients [median (interquartile range) 365 (166) ng/L] compared with controls [244 (142.5) ng/L]. Although the diagnostic performance of VLP-1 alone was comparable to that of Abeta, tTau, or pTau alone, the combination of the 4 biomarkers demonstrated better performance than each individually. VLP-1 concentrations were higher in AD subjects with APOE epsilon4/epsilon4 genotype [599 (240) ng/L] compared with epsilon3/epsilon4 [376 (127) ng/L] and epsilon3/epsilon3 [280 (115.5) ng/L] genotypes. Furthermore, VLP-1 values demonstrated a high degree of correlation with pTau (r = 0.809) and tTau (r = 0.635) but not Abeta(1-42) (r = -0.233). VLP-1 was the only biomarker that correlated with MMSE score (r = -0.384, P = 0.030). Conclusions These results suggest that neuronal injury markers such as VLP-1 may have utility as biomarkers for AD.
Key findings
- We sought to determine if the novel brain injury biomarker, visinin-like protein 1 (VLP-1), is altered in the CSF of AD patients compared with controls, and to compare its values to the other well-studied CSF biomarkers 42-amino acid amyloid-beta peptide (Abeta(1-42)), total Tau (tTau), and hyperphosphorylated Tau (pTau).
- Results CSF VLP-1 concentrations were significantly higher in AD patients [median (interquartile range) 365 (166) ng/L] compared with controls [244 (142.5) ng/L].
- Although the diagnostic performance of VLP-1 alone was comparable to that of Abeta, tTau, or pTau alone, the combination of the 4 biomarkers demonstrated better performance than each individually.
- VLP-1 concentrations were higher in AD subjects with APOE epsilon4/epsilon4 genotype [599 (240) ng/L] compared with epsilon3/epsilon4 [376 (127) ng/L] and epsilon3/epsilon3 [280 (115.5) ng/L] genotypes.
- Furthermore, VLP-1 values demonstrated a high degree of correlation with pTau (r = 0.809) and tTau (r = 0.635) but not Abeta(1-42) (r = -0.233).
Why it matters
CSF levels of the brain injury marker VLP-1 were higher in Alzheimer patients than controls, and combining it with amyloid-beta and tau markers performed better than any one alone. This was a small study of 33 patients and 24 controls, so it does not by itself establish a diagnostic test.
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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 (Clinical chemistry) |
| Journal's citation record | 3 / 4 | Clinical Chemistry: journal h-index 323 (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 | 2008 — within 20 year(s) of the newest study here |
| 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 | 5 / 7 | Cited 126 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 6.3 citations a year over 20 year(s) since 2008 |
| Impact for its field and year | 3 / 6 | Cited 4.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 11 other studies in this library |
| Still being cited | 2 / 4 | Cited 18 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Jack H. Ladenson: h-index 56 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Washington University in St. Louis: institution h-index 1,962 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 18703769) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 46 / 100 | — |
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Read the original
- DOI: 10.1373/clinchem.2008.104497
- PubMed: 18703769
- Original source →
- Free full text: PubMed Central →
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
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APA 7th
Lee, J. M., Blennow, K., Andreasen, N., Laterza, O., Modur, V., Olander, J., et al. (2008). The brain injury biomarker VLP-1 is increased in the cerebrospinal fluid of Alzheimer disease patients. Clinical chemistry. https://doi.org/10.1373/clinchem.2008.104497
Vancouver
Lee JM, Blennow K, Andreasen N, Laterza O, Modur V, Olander J, et al. The brain injury biomarker VLP-1 is increased in the cerebrospinal fluid of Alzheimer disease patients. Clinical chemistry. 2008. doi:10.1373/clinchem.2008.104497. PMID: 18703769.
BibTeX
@article{lee2008-18703769,
author = {Lee, J. M. and Blennow, K. and Andreasen, N. and Laterza, O. and Modur, V. and Olander, J. and Gao, F. and Ohlendorf, M. and others},
title = {{The brain injury biomarker VLP-1 is increased in the cerebrospinal fluid of Alzheimer disease patients}},
journal = {Clinical chemistry},
year = {2008},
doi = {10.1373/clinchem.2008.104497},
pmid = {18703769},
url = {https://doi.org/10.1373/clinchem.2008.104497}
}
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