Publication date: Available online 13 November 2018
Source: Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring
Author(s): Thomas J. Nelson, Abhik Sen
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 HDL-like ApoE particles from 12 AD and 10 control patients using size-exclusion chromatography.
Results
ApoE particles from patients genotyped as E4/E4 were 2.2 ± 0.3 times as massive as particles from E3/E3 control subjects and 1.4 ± 0.1 times as massive as particles from E3/E3 AD patients. The increased particle size was not because of incorporation of amyloid beta or ApoE proteolysis products. Particles from AD patients genotyped as E3/E3 were 1.59 ± 0.27 times as massive as E3/E3 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.