The Cerebrospinal Fluid Profile of Cholesterol Metabolites in Parkinson’s Disease and Their Association With Disease State and Clinical Features

Griffiths, William; Abdel-Khalik, Jonas; Moore, Sarah F.; Wijeyekoon, Ruwani S.; Crick, Peter; Yutuc, Eylan; Farrell, Krista; Breen, David P.; Williams-Gray, Caroline H.; Theofilopoulos, Spyridon; Arenas, Ernest; Trupp, Miles; Barker, Roger A.; Wang, Yuqin

doi:10.3389/fnagi.2021.685594

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The Cerebrospinal Fluid Profile of Cholesterol Metabolites in Parkinson’s Disease and Their Association With Disease State and Clinical Features

William Griffiths

, Jonas Abdel-Khalik, Sarah F. Moore, Ruwani S. Wijeyekoon, Peter Crick, Eylan Yutuc

, Krista Farrell, David P. Breen, Caroline H. Williams-Gray, Spyridon Theofilopoulos

, Ernest Arenas, Miles Trupp, Roger A. Barker, Yuqin Wang

Frontiers in Aging Neuroscience, Volume: 13, Start page: 685594

Swansea University Authors: William Griffiths , Jonas Abdel-Khalik, Peter Crick, Eylan Yutuc , Spyridon Theofilopoulos , Yuqin Wang

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DOI (Published version): 10.3389/fnagi.2021.685594

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-dihydrox...

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Published in:	Frontiers in Aging Neuroscience
ISSN:	1663-4365
Published:	Frontiers Media SA 2021
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URI:	https://cronfa.swan.ac.uk/Record/cronfa57043
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first_indexed	2021-09-22T10:06:08Z
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We found that CSF 7α-hydroxycholesterol levels correlated positively with depression in PD patients, while two presumptively identified cholestenoic acids correlated negatively with depression.</abstract><type>Journal Article</type><journal>Frontiers in Aging Neuroscience</journal><volume>13</volume><journalNumber/><paginationStart>685594</paginationStart><paginationEnd/><publisher>Frontiers Media SA</publisher><placeOfPublication/><isbnPrint/><isbnElectronic/><issnPrint/><issnElectronic>1663-4365</issnElectronic><keywords>sterol, oxysterol, dihydroxycholesterol, bile acid biosynthesis, mass spectrometry</keywords><publishedDay>30</publishedDay><publishedMonth>8</publishedMonth><publishedYear>2021</publishedYear><publishedDate>2021-08-30</publishedDate><doi>10.3389/fnagi.2021.685594</doi><url/><notes/><college>COLLEGE NANME</college><department>Biomedical Sciences</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>BMS</DepartmentCode><institution>Swansea University</institution><apcterm>External research funder(s) paid the OA fee (includes OA grants disbursed by the Library)</apcterm><funders>UKRI Biotechnology and Biological Sciences Research Council, BB/I001735/1; BB/N015932/1; BB/L001942/1</funders><projectreference>BB/I001735/1; BB/N015932/1; BB/L001942/1</projectreference><lastEdited>2022-10-27T10:55:33.7901303</lastEdited><Created>2021-06-07T11:28:04.9560845</Created><path><level id="1">Faculty of Medicine, Health and Life Sciences</level><level id="2">Swansea University Medical School - Medicine</level></path><authors><author><firstname>William</firstname><surname>Griffiths</surname><orcid>0000-0002-4129-6616</orcid><order>1</order></author><author><firstname>Jonas</firstname><surname>Abdel-Khalik</surname><order>2</order></author><author><firstname>Sarah F.</firstname><surname>Moore</surname><order>3</order></author><author><firstname>Ruwani S.</firstname><surname>Wijeyekoon</surname><order>4</order></author><author><firstname>Peter</firstname><surname>Crick</surname><orcid/><order>5</order></author><author><firstname>Eylan</firstname><surname>Yutuc</surname><orcid>0000-0001-9971-1950</orcid><order>6</order></author><author><firstname>Krista</firstname><surname>Farrell</surname><order>7</order></author><author><firstname>David P.</firstname><surname>Breen</surname><order>8</order></author><author><firstname>Caroline H.</firstname><surname>Williams-Gray</surname><order>9</order></author><author><firstname>Spyridon</firstname><surname>Theofilopoulos</surname><orcid>0000-0003-1986-0943</orcid><order>10</order></author><author><firstname>Ernest</firstname><surname>Arenas</surname><order>11</order></author><author><firstname>Miles</firstname><surname>Trupp</surname><order>12</order></author><author><firstname>Roger A.</firstname><surname>Barker</surname><order>13</order></author><author><firstname>Yuqin</firstname><surname>Wang</surname><orcid>0000-0002-3063-3066</orcid><order>14</order></author></authors><documents><document><filename>57043__20962__5f44325c26c346ca8e2aab87009e9f38.pdf</filename><originalFilename>57043.pdf</originalFilename><uploaded>2021-09-22T11:07:35.3177813</uploaded><type>Output</type><contentLength>5493658</contentLength><contentType>application/pdf</contentType><version>Version of Record</version><cronfaStatus>true</cronfaStatus><documentNotes>© 2021 Griffiths, Abdel-Khalik, Moore, Wijeyekoon, Crick, Yutuc, Farrell, Breen, Williams-Gray, Theofilopoulos, Arenas, Trupp, Barker and Wang. 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spelling	2022-10-27T10:55:33.7901303 v2 57043 2021-06-07 The Cerebrospinal Fluid Profile of Cholesterol Metabolites in Parkinson’s Disease and Their Association With Disease State and Clinical Features 3316b1d1b524be1831790933eed1c26e 0000-0002-4129-6616 William Griffiths William Griffiths true false 1ad85bb2d1b5ef373f12a2d3c1889823 Jonas Abdel-Khalik Jonas Abdel-Khalik true false 9e8253a728dc2ad7303ee8928fc85560 Peter Crick Peter Crick true false 99332f073ce913a9b7d8b6441b17516d 0000-0001-9971-1950 Eylan Yutuc Eylan Yutuc true false bcd1bdbdf59d0724d2f9e9a48e671107 0000-0003-1986-0943 Spyridon Theofilopoulos Spyridon Theofilopoulos true false c92729b58622f9fdf6a0e7d8f4ce5081 0000-0002-3063-3066 Yuqin Wang Yuqin Wang true false 2021-06-07 BMS 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. Journal Article Frontiers in Aging Neuroscience 13 685594 Frontiers Media SA 1663-4365 sterol, oxysterol, dihydroxycholesterol, bile acid biosynthesis, mass spectrometry 30 8 2021 2021-08-30 10.3389/fnagi.2021.685594 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University External research funder(s) paid the OA fee (includes OA grants disbursed by the Library) UKRI Biotechnology and Biological Sciences Research Council, BB/I001735/1; BB/N015932/1; BB/L001942/1 BB/I001735/1; BB/N015932/1; BB/L001942/1 2022-10-27T10:55:33.7901303 2021-06-07T11:28:04.9560845 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine William Griffiths 0000-0002-4129-6616 1 Jonas Abdel-Khalik 2 Sarah F. Moore 3 Ruwani S. Wijeyekoon 4 Peter Crick 5 Eylan Yutuc 0000-0001-9971-1950 6 Krista Farrell 7 David P. Breen 8 Caroline H. Williams-Gray 9 Spyridon Theofilopoulos 0000-0003-1986-0943 10 Ernest Arenas 11 Miles Trupp 12 Roger A. Barker 13 Yuqin Wang 0000-0002-3063-3066 14 57043__20962__5f44325c26c346ca8e2aab87009e9f38.pdf 57043.pdf 2021-09-22T11:07:35.3177813 Output 5493658 application/pdf Version of Record true © 2021 Griffiths, Abdel-Khalik, Moore, Wijeyekoon, Crick, Yutuc, Farrell, Breen, Williams-Gray, Theofilopoulos, Arenas, Trupp, Barker and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) true eng http://creativecommons.org/licenses/by/4.0/
title	The Cerebrospinal Fluid Profile of Cholesterol Metabolites in Parkinson’s Disease and Their Association With Disease State and Clinical Features
spellingShingle	The Cerebrospinal Fluid Profile of Cholesterol Metabolites in Parkinson’s Disease and Their Association With Disease State and Clinical Features William Griffiths Jonas Abdel-Khalik Peter Crick Eylan Yutuc Spyridon Theofilopoulos Yuqin Wang
title_short	The Cerebrospinal Fluid Profile of Cholesterol Metabolites in Parkinson’s Disease and Their Association With Disease State and Clinical Features
title_full	The Cerebrospinal Fluid Profile of Cholesterol Metabolites in Parkinson’s Disease and Their Association With Disease State and Clinical Features
title_fullStr	The Cerebrospinal Fluid Profile of Cholesterol Metabolites in Parkinson’s Disease and Their Association With Disease State and Clinical Features
title_full_unstemmed	The Cerebrospinal Fluid Profile of Cholesterol Metabolites in Parkinson’s Disease and Their Association With Disease State and Clinical Features
title_sort	The Cerebrospinal Fluid Profile of Cholesterol Metabolites in Parkinson’s Disease and Their Association With Disease State and Clinical Features
author_id_str_mv	3316b1d1b524be1831790933eed1c26e 1ad85bb2d1b5ef373f12a2d3c1889823 9e8253a728dc2ad7303ee8928fc85560 99332f073ce913a9b7d8b6441b17516d bcd1bdbdf59d0724d2f9e9a48e671107 c92729b58622f9fdf6a0e7d8f4ce5081
author_id_fullname_str_mv	3316b1d1b524be1831790933eed1c26e_*_William Griffiths 1ad85bb2d1b5ef373f12a2d3c1889823__Jonas Abdel-Khalik 9e8253a728dc2ad7303ee8928fc85560__Peter Crick 99332f073ce913a9b7d8b6441b17516d__Eylan Yutuc bcd1bdbdf59d0724d2f9e9a48e671107__Spyridon Theofilopoulos c92729b58622f9fdf6a0e7d8f4ce5081_*_Yuqin Wang
author	William Griffiths Jonas Abdel-Khalik Peter Crick Eylan Yutuc Spyridon Theofilopoulos Yuqin Wang
author2	William Griffiths Jonas Abdel-Khalik Sarah F. Moore Ruwani S. Wijeyekoon Peter Crick Eylan Yutuc Krista Farrell David P. Breen Caroline H. Williams-Gray Spyridon Theofilopoulos Ernest Arenas Miles Trupp Roger A. Barker Yuqin Wang
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container_volume	13
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publisher	Frontiers Media SA
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department_str	Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
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description	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.
published_date	2021-08-30T04:12:28Z
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The Cerebrospinal Fluid Profile of Cholesterol Metabolites in Parkinson’s Disease and Their Association With Disease State and Clinical Features

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