Brain
cholesterol is mainly involved in the cell membrane structure, in signal transduction,
neurotransmitter release, synaptogenesis and membrane trafficking. Impairment of brain
cholesterol metabolism was described in
neurodegenerative diseases, such as
Multiple Sclerosis, Alzheimer and Huntington Diseases. Since the blood-brain barrier efficiently prevents
cholesterol uptake from the circulation into the brain, de novo synthesis is responsible for almost all
cholesterol present there.
Cholesterol is converted into
24S-hydroxycholesterol (24OHC) by
cholesterol 24-hydroxylase (
CYP46A1) expressed in neural cells. Plasma concentration of 24OHC depends upon the balance between cerebral production and hepatic elimination and is related to the number of metabolically active neurons in the brain. Factors affecting brain
cholesterol turnover and liver elimination of
oxysterols, together with the metabolism of plasma
lipoproteins, genetic background, nutrition and lifestyle habits were found to significantly affect its plasma levels. Either increased or decreased plasma 24OHC concentrations were described in patients with
neurodegenerative diseases. A group of evidence suggests that reduced levels of 24OHC are related to the loss of metabolically active cells and the degree of brain
atrophy.
Inflammation, dysfunction of BBB, increased
cholesterol turnover might counteract this tendency resulting in increased levels or, in some cases, in unsignificant changes. The study of plasma 24OHC is likely to offer an insight about brain
cholesterol turnover with a limited diagnostic power.