The Diagnostic Use of the Plasma Quantification of 24S-Hydroxycholesterol and Other Oxysterols in Neurodegenerative Disease

Abstract

Cholesterol regulates fluidity and structure of cellular membranes. The brain is involved in signal transduction, synaptogenesis, and membrane trafficking. An impairment of its metabolism was observed in different neurodegenerative diseases, such as Multiple Sclerosis, Alzheimer, and Huntington diseases. Because of the blood-brain barrier, cholesterol cannot be uptaken from the circulation and all the cholesterol is locally synthetized. The excess cholesterol in neurons is converted into 24S-hydroxycholesterol (24OHC) by the cholesterol 24-hydroxylase (CYP46A1). The plasmatic concentration of 24OHC results in the balance between cerebral production and liver elimination. It is related to the number of metabolically active neurons in the brain. Several factors that affect the brain cholesterol turnover and the liver elimination of oxysterols, the genetic background, nutrition, and lifestyle habits were found to significantly affect plasma levels of 24OHC. Reduced levels of 24OHC were found related to the loss of metabolically active cells and the degree of brain atrophy. The dysfunction of the blood-brain barrier, inflammation, and increased cholesterol turnover might overlap with this progressive reduction giving temporary increased levels of 24OHC.The study of plasma 24OHC is likely to offer an insight into brain cholesterol turnover with a limited diagnostic power.

Keywords: 24S-Hydroxycholesterols; Alzheimer disease; Biomarkers; Cholesterol; Huntington disease; Lipidomic; Mass spectrometry; Multiple sclerosis; Neurodegenerative diseases; Oxysterols; Parkinson disease.