4.4 Article

The level of 24-hydroxycholesteryl esters decreases in plasma of patients with Parkinson's disease

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NEUROSCIENCE LETTERS
卷 672, 期 -, 页码 108-112

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ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2018.02.041

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Parkinson's disease; Oxidative stress; 24-Hydroxycholesteryl esters; Plasma biomarker

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24-hydroxycholesterol (240H-C) is synthesized almost exclusively in neurons. This oxysterol is mostly present as ester form in both cerebrospinal fluid and plasma. The enzyme lecithin-cholesterol acyltransferase esterifles 240H-C in the brain, and the level of 240H-C esters in cerebrospinal fluid was found to be correlated with the level of 240H-C esters in plasma. Decreased levels of 240H-C esters levels were previously found in Alzheimer's disease and Amyotrophic Lateral Sclerosis. This finding was attributed to the inhibitory effect of oxidative stress on lecithin-cholesterol acyltransferase activity in neurodegenerative conditions. Data reported here show that the plasma level of 240H-C esters is decreased also in Parkinson's disease. ROC analysis identified 69.0% of 240H-C esterification as the threshold (AUC = 0.98) discriminating patients (N = 19) from healthy subjects (N = 19) with 100% specificity vs controls, 89.5% sensitivity, 94.7% accuracy, and 100% precision. The level of 240H-C esters was not correlated with UPDRS I or UPDRS III when evaluated at the time of blood sampling. By contrast, it was negatively correlated with UPDRS I (r = - 0.4984, p = 0.0299) after one year of follow up. Therefore, this level might represent a novel biomarker of neurodegeneration in Parkinson's disease. The biomarker level is here proposed as a measure to evaluate the severity of disease, as well as to monitor the progression of this pathology.

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