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Baseline plasma C1q and C3 as potential biomarkers for lecanemab efficacy and ARIA risk in early Alzheimer's disease
Byeon G, Lee JW, Kim S, Um YH, Wang SM, Ha S, Park SY, Shin I et al.. Alzheimer's & dementia (New York, N. Y.), 2026-07-01
Topic: Amyloid, tau and blood-test diagnosis
Introduction The classical complement cascade has been implicated in amyloid beta (Aβ) clearance and in the pathogenesis of amyloid-related imaging abnormalities (ARIA) during anti-amyloid monoclonal antibody therapy. Clinically accessible peripheral biomarkers of this cascade remain uncharacterized in real-world cohorts. Methods We conducted a retrospective, hypothesis-generating cohort study of 62 patients with early Alzheimer's disease initiating lecanemab. ARIA risk was evaluated in the safety cohort ( N = 62), and absolute amyloid reduction at week 26 was evaluated in the efficacy cohort with paired baseline and 26-week amyloid positron emission tomography ( N = 34). Associations of baseline plasma C1q, C3, and apolipoprotein E ε4 ( APOE ε4) carrier status with these outcomes were examined using Firth's penalized logistic regression and bootstrap linear regression (2000 iterations), with prespecified sensitivity analyses. Within-subject changes in C3 ( N = 30) and C1q ( N = 19) were assessed by paired Wilcoxon test. Results Lower baseline C3 was nominally associated with higher ARIA risk (odds ratio [OR] per 1 SD = 0.44, 95% CI: 0.15 to 0.97, p = 0.040, uncorrected), and this association persisted in international normalized ratio (INR)-adjusted and simplified models. C3 ≤ 25th percentile (≤99 mg/dL) showed a trend (OR: 4.78, 95% CI: 0.98 to 26.34, p = 0.052). In the efficacy cohort, higher baseline C1q was associated with smaller amyloid reduction ( β = -6.86, 95% CI: -12.19 to -3.06, p = 0.002); carriers of at least one APOE ε4 allele, a status that in this cohort jointly reflects genotype and dose-titration, showed less amyloid reduction ( β = -19.50, 95% CI -31.57 to -8.40, p < 0.001). Within-subject changes in C1q and C3 were not significant ( p = 0.248 and 0.114, respectively). Discussion Lower baseline C3 was consistently associated with ARIA risk across sensitivity analyses and higher baseline C1q with smaller amyloid reduction at week 26. Findings are exploratory given the limited single-center sample.
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APA 7th
Byeon, G., Lee, J. W., Kim, S., Um, Y. H., Wang, S. M., Ha, S., et al. (2026). Baseline plasma C1q and C3 as potential biomarkers for lecanemab efficacy and ARIA risk in early Alzheimer's disease. Alzheimer's & dementia (New York, N. Y.). https://doi.org/10.1002/trc2.70313
Vancouver
Byeon G, Lee JW, Kim S, Um YH, Wang SM, Ha S, et al. Baseline plasma C1q and C3 as potential biomarkers for lecanemab efficacy and ARIA risk in early Alzheimer's disease. Alzheimer's & dementia (New York, N. Y.). 2026. doi:10.1002/trc2.70313. PMID: 42712875.
BibTeX
@article{byeon2026-42712875,
author = {Byeon, G. and Lee, J. W. and Kim, S. and Um, Y. H. and Wang, S. M. and Ha, S. and Park, S. Y. and Shin, I. and others},
title = {{Baseline plasma C1q and C3 as potential biomarkers for lecanemab efficacy and ARIA risk in early Alzheimer's disease}},
journal = {Alzheimer's \& dementia (New York, N. Y.)},
year = {2026},
doi = {10.1002/trc2.70313},
pmid = {42712875},
url = {https://doi.org/10.1002/trc2.70313}
}
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Key findings
- Results Lower baseline C3 was nominally associated with higher ARIA risk (odds ratio [OR] per 1 SD = 0.44, 95% CI: 0.15 to 0.97, p = 0.040, uncorrected), and this association persisted in international normalized ratio (INR)-adjusted and simplified models.
- In the efficacy cohort, higher baseline C1q was associated with smaller amyloid reduction ( β = -6.86, 95% CI: -12.19 to -3.06, p = 0.002); carriers of at least one APOE ε4 allele, a status that in this cohort jointly reflects genotype and dose-titration, showed less amyloid reduction ( β = -19.50, 95% CI -31.57 to -8.40, p < 0.001).
- Within-subject changes in C1q and C3 were not significant ( p = 0.248 and 0.114, respectively).
- Discussion Lower baseline C3 was consistently associated with ARIA risk across sensitivity analyses and higher baseline C1q with smaller amyloid reduction at week 26.
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Study details
- Study designcohort study
- Participants62
- Effect sizeOR: 4.78
- Evidence strengthModerate
How this study scored 78/100
Published in a leading specialty journal, and it is a cohort study following people over time. Scored zero for randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 45 of the 58 points we could judge it on, which is 78 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Alzheimer's & dementia (New York, N. Y.)) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 1 / 4 | 62 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 42712875) |
| Free to read | 2 / 2 | Free to read |
| Points | 45 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 45 of the 58 points we could judge it on is 78 out of 100. |
| Total | 78 / 100 | — |
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