ApoE influences amyloid-β (Aβ) clearance despite minimal apoE/Aβ association in physiological conditions

Apolipoprotein E gene (APOE) alleles may shift the onset of Alzheimer's disease (AD) through apoE protein isoforms changing the probability of amyloid-β (Aβ) accumulation. It has been proposed that differential physical interactions of apoE isoforms with soluble Aβ (sAβ) in brain fluids influence the metabolism of Aβ, providing a mechanism to account for how APOE influences AD risk. In contrast, we provide clear evidence that apoE and sAβ interactions occur minimally in solution and in the cerebrospinal fluid of human subjects, producing apoE3 and apoE4 isoforms as assessed by multiple biochemical and analytical techniques. Despite minimal extracellular interactions with sAβ in fluid, we find that apoE…

• AH
  American Health Assistance Foundation
• EL
  Eli Lilly and Company
• NI
  National Institutes of Health

  Awards: AG13956, AG027924, NS074969, AG03991
• CF
  Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University in St. Louis