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The associations of cerebrospinal fluid ApoE and C1q with Alzheimer's disease biomarkers
Abstract
Background: The roles of complement 1q (C1q) and Apolipoprotein E (ApoE) in driving Alzheimer's disease (AD) progression might be explained by their associations with neuroinflammation and AD pathology which were previously reported. Objective: We examined the associations of cerebrospinal fluid (CSF) C1q and ApoE with CSF neuroinflammatory biomarkers and AD core biomarkers, as well as explored whether C1q mediated the associations of CSF ApoE with these biomarkers. Methods: Here, we analyzed CSF proteomics data from Alzheimer's Disease Neuroimaging Initiative (ADNI) using two different ADNI proteomics datasets—SomaScan (n = 579)and multiple reaction monitoring (MRM[n = 207]). Linear regression analyses were conducted to explore the association of CSF ApoE and C1q. The mediation model and structural equation model (SEM) were conducted to explore the associations of ApoE and C1q with AD biomarkers. Results: Multiple linear regression showed that CSF ApoE was positively associated with CSF C1q in total participants and Alzheimer's continuum participants. Mediation analyses indicated that C1q mediated the associations of CSF ApoE with CSF T-tau, P-tau, sTREM2 and GFAP (mediation proportions range from 15.06 to 44.64%; all the p values < 0.05) but not with CSF amyloid-β and progranulin (PGRN). The SEM yielded similar results. Conclusions: Our findings suggest that C1q is linked to ApoE, and it mediates the associations of ApoE with T-tau, P-tau, sTREM2, GFAP, indicating C1q association with ApoE might be involved in AD progression.
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CSF levels of C1q correlate with AD.
“Previous reports show a correlation between CSF levels of C1q and AD (84).”
From Lipidome and proteome of astrocyte and microglia ApoE lipoprotein reveal differences based on cell type and ApoE isoform (2026) · cites this paper as [84]
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“34 Increased C1q leads to an increase in the complement protein C3.”
2023 Alzheimer's disease facts and figures
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“47 The binding of C1q to ApoE is thought to initiate CP activation on the surface or reduce activation in solution, and C1q can bind to all ApoE subtypes.”
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Self-citationTREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis
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“38,39 In the presence of both CSF C1q and ApoE, the C1q-ApoE complexes were mentioned in several previous studies, which suggested that the C1q-ApoE interaction and the formation of the complexes played critical roles in their synergistic effects on AD.”
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Strickland, M. R., Wang, Z., Golden, L. R., Wang, H., Lu, P., Ren, Y., Tabor, G. T., Zhao, N., Ulrich, J. D., Han, X., et al. (2026) · Journal of Lipid Research · doi:10.1016/j.jlr.2026.101000 · Cited by 8
Self-citation
Metadata
- Authors
- Lin, Y.-J., Liu, Y., Sheng, Z.-H., Fu, Y., Ma, L.-Z., Zhang, Z.-H., Wang, L.-Y., Huang, L.-Y., Liu, M., Wang, Z.-T., Tan, L., & *, F. T. A. D. N. I.
- Affiliations
- School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, China
- Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
- Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing, China
- Department of Neurology, Qingdao Municipal Hospital, Dalian Medical University, Dalian, China
- Venue
- Journal of Alzheimer’s Disease
- Publisher
- SAGE Publications
- Published
- 2025-03-17
- Volume
- 104
- Issue
- 3
- Pages
- 852-861
- ISSN
- 1387-2877
- 1875-8908
- Cited by
- 3
- References
- 14
- Language
- en
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