The mouse C1q A-chain sequence alters beta-amyloid-induced complement activation

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 activatio n of complement (C') by beta-amyloid (A beta). A beta has been shown to act ivate C' by binding to a site on the Clq A-chain. The mouse A-chain sequenc e differs significantly from human, and a peptide based on the mouse A-chai n sequence was ineffective at blocking activation of C' by A beta in contra st to the inhibition seen with the human peptide. Comparison of mouse and h uman serum showed that human C' was activated more effectively by A beta th an was mouse C'. Therefore, additional genetic manipulations may be necessa ry to replicate in the murine model the inflammation and neurodegeneration that occur in AD. (C) 1999 Elsevier Science Inc. All rights reserved.