Cholesterol synthesis rate in human hippocampus declines with aging

Abstract

During the last three to four decades, interest in the interaction of circulating and brain cholesterol has increased. As the CNS matures and cholesterol pools in the brain become constant, the rate of de novo synthesis of cholesterol in the brain is expected to decline. We measured cholesterol, its precursors and its brain specific metabolite 24S-hydroxycholesterol in hippocampus from 7 female and 13 male corpses by highly sensitive and specific gas chromatography–mass spectrometry. Two age groups (young, n = 10; elderly, n = 10) were formed with a cut-off at the median age of 38 years. The amount of cholesterol was comparable in young and elderly subjects. The concentrations of the cholesterol precursors lanosterol and lathosterol were significantly higher in young ( P = 0.036 and 0.005, respectively) than in elderly subjects. In accordance, there was a significantly negative correlation between age and lathosterol concentrations ( r = −0.505; P = 0.023). Absolute levels of 24S-hydroxycholesterol in the brain were slightly, but not significantly, lower in the hippocampal specimens from the elderly subjects. We conclude that during aging, cholesterol synthesis is decreased in the hippocampus, while absolute cholesterol content remains at a stable level.