Apolipoprotein E4 (ApoE4) but not ApoE3 or ApoE2 potentiates beta-amyloid protein activation of complement in vitro.
Apolipoprotein E4 (ApoE4) increases the risk of late-onset Alzheimer's disease (AD). It binds tightly to beta-amyloid protein (A beta), which is known to activate the classical complement pathway in vitro. Since complement activation is a possible mechanism for promoting inflammation in AD, we tested, utilizing ELISA techniques, whether the various isoforms of ApoE could influence A beta complement activation, or could themselves activate the pathway. A beta applied alone to ELISA plate wells at concentrations of 100-500 ng showed a linear increase in ability to activate serum complement, but all the ApoE isoproteins were inactive. When 200 or 430 ng of A beta were plated and then exposed to solutions of 100-200 ng of ApoE2, ApoE3, ApoE4 or bovine serum albumin (BSA), only ApoE4 significantly enhanced the activation. This ApoE4-specific enhancement of complement activation by A beta may relate to its role in increasing the risk of late-onset AD.
McGeer
P L
PL
Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, Canada. plmcgeer@unixg.ubc.ca
Walker
D G
DG
Pitas
R E
RE
Mahley
R W
RW
McGeer
E G
EG
D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000494:pharmacology*; D003167:Complement Activation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans
D016229:Amyloid beta-Peptides; D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E