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.
The level of 24-hydroxycholesteryl esters decreases in plasma of patients with Parkinson's disease / Di Natale, Concetta; Monaco, Alessandra; Pedone, Carlo; Tessitore, Alessandro; De Mase, Antonio; Tedeschi, Gioacchino; Netti, Paolo Antonio; Abrescia, Paolo. - In: NEUROSCIENCE LETTERS. - ISSN 0304-3940. - 672:(2018), pp. 108-112. [10.1016/j.neulet.2018.02.041]
The level of 24-hydroxycholesteryl esters decreases in plasma of patients with Parkinson's disease
Di Natale, Concetta;MONACO, ALESSANDRA;Pedone, Carlo;Netti, Paolo Antonio;Abrescia, Paolo
2018
Abstract
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.