Associations between plasma complement C1q and cerebrospinal fluid biomarkers of Alzheimer’s disease pathology in cognitively intact adults: The CABLE study

BackgroundC1q is a promoter of the classical pathway of complement and its massive expression may be associated with the development of Alzheimer's disease (AD). However, the relationships between C1q and the major pathological challenges, including amyloid-β (Aβ) and tau deposition, remain undetermined in the preclinical AD phase.ObjectiveThis study aims to investigate the connections between plasma C1q and CSF AD biomarkers.MethodsThe cognitively intact participants (N = 1264) from the Chinese Alzheimer's Biomarker and LifestylE (CABLE) study were categorized into four groups, including Stage 0 [normal Amyloid-β_1-42 (Aβ_1-42), Phosphorylated-tau (P-tau) and Total-tau (T-tau)], Stage 1 (abnormal Aβ_1-42, but normal P-tau or T-tau), Stage 2 (abnormal Aβ_1-42 and abnormal P-tau or T-tau), and suspected non-Alzheimer disease pathology (SNAP) (abnormal P-tau or T-tau, but normal amyloid levels). The changes in plasma C1q levels among these groups and the correlation between C1q levels and cerebrospinal fluid (CSF) AD biomarkers were performed.ResultsThe results demonstrated plasma C1q levels are lower in Stage 0 (p = 0.010) and SNAP (p < 0.001) compared with Stage 1. A significant association between C1q levels and CSF AD pathology, including Aβ_1-42 (β = -0.143, p < 0.001), Aβ_1-42/Aβ_1-40 (β = -0.173, p < 0.001), P-tau/Aβ_1-42 (β = 0.156, p < 0.001), and T-tau/Aβ_1-42 (β = 0.130, p < 0.001) has been identified.ConclusionsThe current research elucidates a positive correlation between elevated plasma C1q levels and CSF Aβ pathology, with C1q amplifying concomitantly with the pathological and clinical progression of AD.