Correlation analysis between complement proteins and Alzheimer's disease
Ying-Tong Lu, Zi-Ming Guo, Meng-Yuan Liu, Cheng-Hong Ji, Yu-Ting Luo, Shu-Yun Zhou, Tao Ma, Xi-Chen Zhu,Background
The prominent pathological features of Alzheimer's disease (AD) are amyloid-β (Aβ) plaques and tau pathology. The complement cascade is closely related to AD-associated pathological processes; however, the precise mechanisms underlying its contributions remain incompletely elucidated.
Objective
We aim to investigate the changes in complement protein expression during AD progression.
Methods
This study enrolled 285 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Participants were classified into biomarker-defined groups based on predefined cutoff values for Aβ 42 and phosphorylated tau (P-tau). We compared cerebrospinal fluid (CSF) levels of complement proteins (C1q, C2, C3, C4a, C5, C6, C8b, and factor B) across these subgroups. Furthermore, we explored their associations with core AD biomarkers (Aβ 42 , P-tau, and T-tau) and clinical characteristics. Additionally, we investigated age-related changes in complement gene expression within the cerebral cortex of 3xTg mice using single-nucleus RNA sequencing.
Results
Complement protein levels in the CSF of A + subjects were significantly lower than those in A− subjects, and complement protein levels were positively correlated with Aβ pathology. Complement protein levels were influenced by factors such as age, gender, body mass index,
Conclusions
Complement proteins undergo significant changes during the pathogenesis of AD, and alterations in their levels may reflect early pathological changes in AD and warrant further investigation. Notably, our findings suggest that microglia may contribute to complement-mediated pathological processes associated with AD.