The mouse C1q A-chain sequence alters beta-amyloid-induced complement activationsmall star, filled

In transgenic models of Alzheimer’s disease (AD) neuronal loss has not been widely observed. The loss of neurons in AD may be due to chronic activation of complement (C’) by beta-amyloid (Aβ). Aβ has been shown to activate C’ by binding to a site on the C1q A-chain. The mouse A-chain sequence differs significantly from human, and a peptide based on the mouse A-chain sequence was ineffective at blocking activation of C’ by Aβ in contrast to the inhibition seen with the human peptide. Comparison of mouse and human serum showed that human C’ was activated more effectively by Aβ than was mouse C’. Therefore, additional genetic manipulations may be necessary to replicate in the murine model the inflammation and neurodegeneration that occur in AD.