Correlation analysis between complement proteins and Alzheimer's disease
Ying-Tong Lu1, Zi-Ming Guo1, Meng-Yuan Liu1
1Department of Neurology, the Wuxi No. 2 People's Hospital, Jiangnan University Medical Center, Wuxi, China.
Journal of Alzheimer'S Disease : JAD
|August 12, 2026
Summary
Alzheimer's disease (AD) involves changes in complement proteins, which may indicate early pathology. Microglia appear to play a role in these complement-mediated processes in AD.
Area of Science:
- Neuroscience
- Immunology
- Biochemistry
Background:
- Alzheimer's disease (AD) is characterized by amyloid-β (Aβ) plaques and tau pathology.
- The complement cascade's role in AD pathogenesis requires further elucidation.
Purpose of the Study:
- Investigate complement protein expression changes during Alzheimer's disease progression.
- Explore associations between complement proteins, AD biomarkers, and clinical features.
Main Methods:
- Analyzed cerebrospinal fluid (CSF) complement protein levels in 285 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort.
- Classified participants into biomarker-defined groups based on Aβ42 and phosphorylated tau (P-tau) levels.
- Examined age-related complement gene expression in mouse models using single-nucleus RNA sequencing.
Main Results:
- CSF complement protein levels were lower in Aβ-positive subjects and correlated positively with Aβ pathology.
- Complement protein levels were influenced by age, gender, BMI, APOE genotype, and hypertension.
- The complement gene C1qa was upregulated in microglia throughout the pathological cycle in 3xTg AD mice.
Conclusions:
- Complement proteins exhibit significant alterations during AD pathogenesis, potentially reflecting early pathological changes.
- Microglia may contribute to complement-mediated pathological processes in Alzheimer's disease.
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