Decreased content, rate of synthesis and export of cholesterol in the brain of apoE knockout mice.

Abstract

Apolipoprotein E knockout (apoE-KO) mice present synaptic loss, cognitive dysfunction, and high plasma lipid levels that may affect brain function simulating Alzheimer disease. Plasma and brain sterols were measured in apoE-KO and in wild type control mice on a cholesterol-free, phytosterol-containing diet by gas chromatography coupled to a mass spectrometer. Plasma cholesterol and phytosterols (campesterol and sitosterol) were higher in apoE-KO compared to control mice. Cholesterol precursors (desmosterol and lathosterol) were not detected in plasma of control mice but were present in apoE-KO mice. In the brain amounts of cholesterol, desmosterol, campesterol and 24-hydroxycholesterol were significantly lower in apoE-KO than in controls. There is a tendency in apoE-KO for lower values of 7α-hydroxycholesterol and 7β-hydroxycholesterol. Cholesterol content, synthesis rates (desmosterol) and export of 24-hydroxycholesterol are reduced in the brain of the severe hypercholesterolemic apoE-KO mice.