The Cerebrospinal Fluid Profile of Cholesterol Metabolites in Parkinson’s Disease and Their Association With Disease State and Clinical Features
William J. Griffiths, Jonas Abdel‐Khalik, Sarah F. Moore, Ruwani Wijeyekoon, Peter J. Crick, Eylan Yutuc, Krista Farrell, David P. Breen, Caroline H. Williams‐Gray, Spyridon Theofilopoulos, Ernest Arenas, Miles Trupp, Roger A. Barker, Yuqin Wang
Abstract
Disordered cholesterol metabolism is linked to neurodegeneration. In this study we investigated the profile of cholesterol metabolites found in the cerebrospinal fluid (CSF) of Parkinson's disease (PD) patients. When adjustments were made for confounding variables of age and sex, 7α,(25R)26-dihydroxycholesterol and a second oxysterol 7α,x,y-trihydroxycholest-4-en-3-one (7α,x,y-triHCO), whose exact structure is unknown, were found to be significantly elevated in PD CSF. The likely location of the additional hydroxy groups on the second oxysterol are on the sterol side-chain. We found that CSF 7α-hydroxycholesterol levels correlated positively with depression in PD patients, while two presumptively identified cholestenoic acids correlated negatively with depression.