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CSF complement 3 and factor H are staging biomarkers in Alzheimer's disease
Hu WT, Watts KD, Tailor P, Nguyen TP, Howell JC, Lee RC, Seyfried NT, Gearing M et al.. Acta neuropathologica communications, 2016-02-17
Topic: Amyloid, tau and blood-test diagnosis
Introduction CSF levels of established Alzheimer's disease (AD) biomarkers remain stable despite disease progression, and non-amyloid non-tau biomarkers have the potential of informing disease stage and progression. We previously identified complement 3 (C3) to be decreased in AD dementia, but this change was not found by others in earlier AD stages. We hypothesized that levels of C3 and associated factor H (FH) can potentially distinguish between mild cognitive impairment (MCI) and dementia stages of AD, but we also found their levels to be influenced by age and disease status. Results We developed a biochemical/bioinformatics pipeline to optimize the handling of complex interactions between variables in validating biochemical markers of disease. We used data from the Alzheimer's Disease Neuro-imaging Initiative (ADNI, n = 230) to build parallel machine learning models, and objectively tested the models in a test cohort (n = 73) of MCI and mild AD patients independently recruited from Emory University. Whereas models incorporating age, gender, APOE ε4 status, and CSF amyloid and tau levels failed to reliably distinguish between MCI and mild AD in ADNI, introduction of CSF C3 and FH levels reproducibly improved the distinction between the two AD stages in ADNI (p Conclusions We propose that CSF C3 and FH alterations may reflect stage-associated biomarker changes in AD, and can complement clinician diagnosis in diagnosing and staging AD using the publically available ADNI database as reference.
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APA 7th
Hu, W. T., Watts, K. D., Tailor, P., Nguyen, T. P., Howell, J. C., Lee, R. C., et al. (2016). CSF complement 3 and factor H are staging biomarkers in Alzheimer's disease. Acta neuropathologica communications. https://doi.org/10.1186/s40478-016-0277-8
Vancouver
Hu WT, Watts KD, Tailor P, Nguyen TP, Howell JC, Lee RC, et al. CSF complement 3 and factor H are staging biomarkers in Alzheimer's disease. Acta neuropathologica communications. 2016. doi:10.1186/s40478-016-0277-8. PMID: 26887322.
BibTeX
@article{hu2016-26887322,
author = {Hu, W. T. and Watts, K. D. and Tailor, P. and Nguyen, T. P. and Howell, J. C. and Lee, R. C. and Seyfried, N. T. and Gearing, M. and others},
title = {{CSF complement 3 and factor H are staging biomarkers in Alzheimer's disease}},
journal = {Acta neuropathologica communications},
year = {2016},
doi = {10.1186/s40478-016-0277-8},
pmid = {26887322},
url = {https://doi.org/10.1186/s40478-016-0277-8}
}
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Key findings
- Results We developed a biochemical/bioinformatics pipeline to optimize the handling of complex interactions between variables in validating biochemical markers of disease.
Why it matters
This study used data from the Alzheimer's Disease Neuroimaging Initiative and an independent test cohort to build machine learning models incorporating CSF complement 3 and factor H levels. Introduction of these levels reproducibly improved the distinction between mild cognitive impairment and mild Alzheimer's disease stages, suggesting they may reflect stage-associated biomarker changes.
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Study details
- Participants230
- Evidence strengthModerate
How this study scored 45/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Acta neuropathologica communications) |
| Journal's citation record | 1 / 4 | Acta Neuropathologica Communications: journal h-index 129 (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 | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2016 — within 20 year(s) of the newest study here |
| Sample size | 2 / 4 | 230 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 | 4 / 7 | Cited 45 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 3.8 citations a year over 12 year(s) since 2016 |
| Impact for its field and year | 2 / 6 | Cited 2.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 1 / 4 | Cited 13 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Eva K. Lee: h-index 36 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Emory University: institution h-index 1,360 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 26887322) |
| Free to read | 2 / 2 | Free to read |
| Total | 45 / 100 | — |
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Read the original
- DOI: 10.1186/s40478-016-0277-8
- PubMed: 26887322
- Original source →
- Free full text: Acta Neuropathologica Communications →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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