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The effect of APOE genotype on brain levels of oxysterols in young and old human APOE epsilon2, epsilon3 and epsilon4 knock-in mice

journal contribution
posted on 2023-05-17, 12:45 authored by Jenner, AM, Lim, WLF, Ng, MP, Wenk, MR, Shui, G, Matthew SharmanMatthew Sharman, Gandy, SE, Martins, RN
Despite apolipoprotein E's important role in cholesterol transport and metabolism in the brain as well as its influence on Alzheimer's disease, the impact of the human APOE genotype on cholesterol metabolism in brain has not been fully examined. This study was carried out to investigate APOE genotype effects on oxysterols measured. In this study the measurement of cholesterol and several oxysterols in the brains of human APOE epsilon2, epsilon3 and epsilon4 knock-in mice at 8 weeks and 1 year of age using gas chromatography mass spectrometry (GC-MS) demonstrated no APOE genotype or age effect on total brain cholesterol and the oxysterol 24-hydroxycholesterol. The level of 27-hydroxycholesterol was elevated in 1 year old animals for all APOE genotypes. Interestingly, lathosterol an indicator of cholesterol synthesis was significantly reduced in the 1 year old animals for all APOE genotypes. APOE epsilon4 expressing mice exhibited statistically lower levels of lathosterol compared to APOE epsilon2 in both the young and old mice. Oxidized cholesterol metabolites were significantly lower in APOE epsilon2 mice compared to other genotypes at 8 weeks old. Although minimal differences were observed between APOE E3 and E4 knock-in (KI) mice, these findings indicate that there are some clear APOE genotype specific effects on brain cholesterol synthesis and associated metabolic pathways, particularly in APOE epsilon2 KI mice.

History

Publication title

Neuroscience: An International Journal

Volume

169

Pagination

109-115

ISSN

0306-4522

Department/School

School of Health Sciences

Publisher

Pergamon-Elsevier Science Ltd

Place of publication

The Boulevard, Langford Lane, Kidlington, Oxford, England, Ox5 1Gb

Rights statement

Copyright 2010 IBRO

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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