Apolipoprotein E particle size is increased in Alzheimer's disease

Abstract

Abstract 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.

Keywords

• ApoE
• apolipoprotein E
• HDL
• Alzheimer's disease
• Size‐exclusion HPLC