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.