Effects of human apolipoprotein E isoforms on the amyloid beta-protein concentration and lipid composition in brain low-density membrane domains.
Apolipoprotein E4 (apoE4) encoded by epsilon 4 allele is a strong genetic risk factor for Alzheimer's disease (AD). ApoE4 carriers have accelerated amyloid beta-protein (A beta) deposition in their brains, which may account for their unusual susceptibility to AD. We hypothesized that the accelerated A beta deposition in the brain of apoE4 carriers is mediated through cholesterol-enriched low-density membrane (LDM) domains. Thus, the concentrations of A beta and various lipids in LDM domains were quantified in the brains of homozygous apoE3 and apoE4 knock-in (KI) mice, and in the brains of those mice bred with beta-amyloid precursor protein (APP) transgenic mice (Tg2576). The A beta 40 and A beta 42 concentrations and the A beta 42 proportions in LDM domains did not differ between apoE3 and apoE4 KI mice up to 18 months of age. The A beta 40 concentration in the LDM domains was slightly, but significantly higher in apoE3/APP mice than in apoE4/APP mice. The lipid composition of LDM domains was modulated in an apoE isoform-specific manner, but its significance for A beta deposition remains unknown. These data show that the apoE isoform-specific effects on the A beta concentration in LDM domains do not occur in KI mouse models.
Morishima-Kawashima
Maho
M
Department of Neuropathology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
Han
Xianlin
X
Tanimura
Yu
Y
Hamanaka
Hiroki
H
Kobayashi
Mariko
M
Sakurai
Takashi
T
Yokoyama
Minesuke
M
Wada
Koji
K
Nukina
Nobuyuki
N
Fujita
Shinobu C
SC
Ihara
Yasuo
Y
D000367:Age Factors; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D001923:Brain Chemistry / Q000235:genetics*; D002531:Cerebellum / Q000648:ultrastructure; D006801:Humans; D008055:Lipids / Q000032:analysis*; D008297:Male; D008566:Membranes / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments; D020033:Protein Isoforms / Q000378:metabolism; D018709:Statistics, Nonparametric
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; D008055:Lipids; D010446:Peptide Fragments; D020033:Protein Isoforms