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

• DOI: 10.1177/13872877251322808
• Publication Date: 2025-03-26T22:14:44Z
• Authors: Rong-Ji Xue; Pei-Yang Gao; Yan-Ming Chen; Ying Liu; Bao-Lin Han; Yi-Ming Huang; Yin-Chu Mi; Rui-Ping Cui; Yu-Jing Lin; Zuo-Teng Wang; Chen-Chen Tan; Ya-Nan Ou; Lan Tan

Background C1q 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.

Objective This study aims to investigate the connections between plasma C1q and CSF AD biomarkers.

Methods

The 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.

Results

The 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.

Conclusions The 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.