Apolipoprotein E particle size is increased in Alzheimer's disease

Introduction: Apolipoprotein E4 (apoE4) is the predominant risk factor for late-onset Alzheimer's disease (AD), but the question of which structural differences might explain its effect remains unclear. Methods: We compared high-density lipoprotein-like apoE particles from 12 AD and 10 control patients using size-exclusion chromatography. Results: ApoE particles from patients genotyped as epsilon 4/epsilon 4 were 2.2 +/- 0.3 times as massive as particles from epsilon 3/epsilon 3 control subjects and 1.4 +/- 0.1 times as massive as particles from epsilon 3/epsilon 3 AD patients. The increased particle size was not because of incorporation of amyloid beta or apoE proteolysis products. Particles from AD patients genotyped as epsilon 3/epsilon 3 were 1.59 +/- 0.27 times as massive as epsilon 3/epsilon 3 control subjects. Discussion: Increased particle size in AD is affected by APOE genotype and by disease-related differences in assembly or stability. These differences suggest that lipoprotein assembly or stability in AD brain plays an important role in determining apoE4 pathogenicity. (C) 2018 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association.