Apolipoprotein E4 (ApoE4) but not ApoE3 or ApoE2 potentiates beta-amyloid protein activation of complement in vitro

Brain Res. 1997 Feb 21;749(1):135-8. doi: 10.1016/s0006-8993(96)01324-8.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / pharmacology*
  • Apolipoprotein E2
  • Apolipoprotein E3
  • Apolipoprotein E4
  • Apolipoproteins E / pharmacology*
  • Complement Activation / drug effects*
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Enzyme-Linked Immunosorbent Assay
  • Humans

Substances

  • Amyloid beta-Peptides
  • Apolipoprotein E2
  • Apolipoprotein E3
  • Apolipoprotein E4
  • Apolipoproteins E