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Influence of APOE genotype and the presence of Alzheimer's pathology on synaptic membrane lipids of human brains
Author(s) -
Oikawa Naoto,
Hatsuta Hiroyuki,
Murayama Shigeo,
Suzuki Akemi,
Yanagisawa Katsuhiko
Publication year - 2014
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.23341
Subject(s) - apolipoprotein e , allele , genotype , cholesterol , pathological , biology , alzheimer's disease , endocrinology , medicine , pathology , neuroscience , disease , biochemistry , gene
The APOE genotype is the major risk factor for Alzheimer's disease (AD); however, it remains unclarified how the ε4 allele accelerates whereas the ε2 allele suppresses AD development, compared with the more common ε3 allele. On the basis of the previous finding that the assembly of the amyloid‐β protein (Aβ) into fibrils in the brain, an early and invariable pathological feature of AD, depends on the lipid environment, we determined the levels of synaptic membrane lipids in aged individuals of different APOE genotypes. In the comparison between amyloid‐free ε2/ε3 and ε3/ε3 brains, the presence of the ε2 allele significantly decreased the level of cholesterol. Alternatively, in the comparison among ε3/ε3 brains, the presence of AD pathology substantially decreased the levels of cholesterol. This study suggests that the ε2 allele suppresses the initiation of AD development by lowering the cholesterol levels in synaptic membranes. © 2014 Wiley Periodicals, Inc.