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 ε4/ε4 were 2.2 ± 0.3 times as massive as particles from ε3/ε3 control subjects and 1.4 ± 0.1 times as massive as particles from ε3/ε3 AD patients. The increased particle size was not because of incorporation of amyloid β or apoE proteolysis products. Particles from AD patients genotyped as ε3/ε3 were 1.59 ± 0.27 times as massive as ε3/ε3 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.