Complement C4A and C4B gene copy number study in Alzheimer's disease patients

Background/Objectives: Increasing evidence suggests the importance of neuroinflammation in the pathogenesis of Alzheimer’s disease (AD), which is a complex neurodegenerative disorder. Complement activation occurs in the brain of patients with AD and seems to contribute to an important local inflammatory state. Increased expression of the fourth serum complement component 4 (C4) has been observed in AD patients in many studies. This protein has two isoforms, encoded by two genes: C4A and C4B localized to the HLA class III region. These genes exhibit copy number variations (CNVs) and this different gene copy number can influence C4 protein levels. We focalized our attention on these two genes, determining the distribution of CNVs in AD patients, compared with healthy controls, in order to analyse their possible involvement in AD pathogenesis. Methods: We investigated 191 AD patients and 300 healthy controls. The C4A and C4B copy numbers were assessed by quantitative PCR (qPCR). Results: The results obtained showed a statistically significant increase in the number of copies for both C4A and C4B in AD patients, compared with healthy controls (p<0,001). Conclusion: The presence of high C4A and C4B copy numbers in AD patients could explain the increased C4 protein expression observed in AD patients, thus highlighting a possible role for C4A and C4B CNVs in the risk of developing AD.