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Systemic complement factors in aging, Alzheimer's disease and other dementias: a longitudinal study over 10 years
Fu X, Cai H, Quan S, Zhang W, Geng Y, Tian Q, Ren Z, Xu Y, An C, Li J, Chu C, Wang W, et al.. Molecular Neurodegeneration, 2026-01-12
Topic: Risk, prevention and care in population studies
Background Complement dysregulation is increasingly recognized in Alzheimer's disease (AD). However, the temporal profile of complement alterations preceding AD onset and their distinction from age-related immune changes remain poorly defined. Clarifying these dynamics could provide insights into AD pathogenesis and identify systemic factors that predict disease onset and progression. Methods We conducted a study involving two cohorts: a longitudinal cohort (n = 235; all cognitively normal at baseline) and a cross-sectional cohort (n = 323; including 53 with AD, 54 with vascular dementia, 51 with Parkinson's disease dementia, 56 with behavioral variant frontotemporal dementia, and 52 with dementia with Lewy bodies). Plasma levels of 14 complement factors were assessed every 2 years over a 10-year follow-up period in the longitudinal cohort and once in the cross-sectional cohort. Results In the longitudinal cohort, aging was accompanied by gradual reductions in C4, C4b, Factor I, and Properdin and by increases in Factor D. These changes were more pronounced in individuals who subsequently developed AD. Importantly, this pattern of complement alterations was detectable during the preclinical and clinical phases of AD but was not observed in other dementias. In the cross-sectional cohort, the same complement profile was specific to AD and distinguished it from other dementia subtypes. Conclusions The results of this study indicate an AD-specific peripheral complement signature associated with disease development, highlighting complement factors as critical immune mediators that link aging and AD. This signature implicates complement factors as promising systemic markers for early detection and potential therapeutic targeting in preclinical AD.
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APA 7th
Fu, X., Cai, H., Quan, S., Zhang, W., Geng, Y., Tian, Q., et al. (2026). Systemic complement factors in aging, Alzheimer's disease and other dementias: a longitudinal study over 10 years. Molecular Neurodegeneration. https://doi.org/10.1186/s13024-026-00927-3
Vancouver
Fu X, Cai H, Quan S, Zhang W, Geng Y, Tian Q, et al. Systemic complement factors in aging, Alzheimer's disease and other dementias: a longitudinal study over 10 years. Molecular Neurodegeneration. 2026. doi:10.1186/s13024-026-00927-3. PMID: 41526986.
BibTeX
@article{fu2026-41526986,
author = {Fu, X. and Cai, H. and Quan, S. and Zhang, W. and Geng, Y. and Tian, Q. and Ren, Z. and Xu, Y. and An, C. and Li, J. and Chu, C. and Wang, W. and others},
title = {{Systemic complement factors in aging, Alzheimer's disease and other dementias: a longitudinal study over 10 years}},
journal = {Molecular Neurodegeneration},
year = {2026},
doi = {10.1186/s13024-026-00927-3},
pmid = {41526986},
url = {https://doi.org/10.1186/s13024-026-00927-3}
}
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Key findings
- Results In the longitudinal cohort, aging was accompanied by gradual reductions in C4, C4b, Factor I, and Properdin and by increases in Factor D.
- Conclusions The results of this study indicate an AD-specific peripheral complement signature associated with disease development, highlighting complement factors as critical immune mediators that link aging and AD.
Why it matters
Over 10 years, a specific pattern of complement protein changes in blood appeared more strongly in people who later developed Alzheimer's and was not seen in other dementias. This identifies possible predictive markers, but it does not show that measuring or altering these factors prevents or treats the disease.
Study details
- Study designcohort
- Participants558
- Evidence strengthModerate
Limitations
Measurements were made in peripheral plasma, which may not reflect complement activity in the brain unless blood-brain barrier integrity is compromised; causality cannot be inferred from observational data; and lifestyle factors such as diet, exercise, smoking and alcohol that modulate immune function were not systematically included.
How this study scored 52/100
Published in a peer-reviewed journal, and it is a cohort study following people over time. Scored zero for effect reported and randomised / blinded because the record does not state it. We have no data on senior author's track record and free to read, so those were left out: it earned 49 of the 94 points we could judge it on, which is 52 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Molecular Neurodegeneration) |
| Journal's citation record | 2 / 4 | Molecular Neurodegeneration: journal h-index 164 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A cohort study following people over time |
| 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 | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 2 / 4 | 558 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 | 1 / 7 | Cited 3 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 4 / 6 | Cited 14.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 3 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | OpenAlex's profile for last-listed author Longfei Jia holds only 5 work(s), too few to judge a track record — left out of this score |
| Institution's track record | 0 / 3 | Capital Medical University: institution h-index 643 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41526986) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 49 / 94 | Scored on 18 of 20 parts. We have no data for the rest, so they are left out: 49 of the 94 points we could judge it on is 52 out of 100. |
| Total | 52 / 100 | — |
What each of these 20 components measures, and what this score is not →
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