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Apolipoprotein E particle size is increased in Alzheimer's disease
1Center for Neurodegenerative Diseases, Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV, USA.
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 A PO E 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.