Complement C1q is associated with neuroinflammation and mediates the association between amyloid-β and tau pathology in Alzheimer’s disease
Bibliographic record
Abstract
Complement C1q initiates the classical complement pathway and becomes activated in Alzheimer’s disease (AD), contributing to the association between amyloid-β (Aβ) and tau pathologies. However, whether C1q influences AD pathology by modulating glial cell communication is unclear. We included 217 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database to explore the associations of cerebrospinal fluid (CSF) C1q with soluble triggering receptor expressed on myeloid cells 2 (sTREM2), glial fibrillary acidic protein (GFAP) and AD biomarkers. Additionally, we incorporated data from 535 participants in the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) study to explore associations. We employed 10,000 bootstrapped iterations of causal mediation analysis to examine the possible mediating role of sTREM2 or GFAP in the relationship between CSF C1q and AD pathology. We found that CSF rather than serum C1q were positively associated with CSF sTREM2, GFAP, Aβ42, phosphorylated-tau (P-tau) and total tau (T-tau) at baseline. CSF C1q was only longitudinally associated with CSF T-tau levels and AD assessment scale-cognitive subscale 13 (ADAS-Cog 13) scores. Mediation analysis demonstrated that Aβ pathology partly mediated the association between CSF C1q and sTREM2 levels, which in turn impacted tau pathology progression. Serum C1q showed a significant association with CSF sTREM2 at baseline as well. C1q is associated with CSF sTREM2 and mediates the relationship between Aβ and tau pathologies. This suggests that C1q may play a crucial role in the progression from Aβ pathology to tau pathology.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.006 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".