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24S-Hydroxycholesterol Correlates With Tau and Is Increased in Cerebrospinal Fluid in Parkinson's Disease and Corticobasal Syndrome
24S-hydroxycholesterol (24OHC) and Tau are produced in neuronal cells and neurodegeneration leads to increased flux of both of them into cerebrospinal fluid (CSF). In the present study, CSF levels of 24OHC and 27S-hydroxycholesterol (27OHC) along with those of Tau, P-Thr(181)-Tau and Aβ(42) were mea...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6137204/ https://www.ncbi.nlm.nih.gov/pubmed/30245667 http://dx.doi.org/10.3389/fneur.2018.00756 |
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author | Björkhem, Ingemar Patra, Kalicharan Boxer, Adam L. Svenningsson, Per |
author_facet | Björkhem, Ingemar Patra, Kalicharan Boxer, Adam L. Svenningsson, Per |
author_sort | Björkhem, Ingemar |
collection | PubMed |
description | 24S-hydroxycholesterol (24OHC) and Tau are produced in neuronal cells and neurodegeneration leads to increased flux of both of them into cerebrospinal fluid (CSF). In the present study, CSF levels of 24OHC and 27S-hydroxycholesterol (27OHC) along with those of Tau, P-Thr(181)-Tau and Aβ(42) were measured in patients with early Parkinson's disease (PD), Corticobasal syndrome (CBS), Corticobasal Degeneration (CBD), and controls. Using mouse models with increased or no formation of Tau protein and increased production of 24OHC, we have also tested the hypothesis that there is a direct association between neuronal turnover of 24OHC and Tau. The levels of 24OHC are increased, at a group level, in patients with PD or CBS. We found significant correlations between levels of 24OHC and Tau or P-Thr(181)-Tau in CSF from patients with PD, CBS or CBD. There were no similar correlations between 24OHC and Aβ(42) in CSF from these patients. The neuronal levels of 24OHC were not altered in Tau knockout or Tau overexpressing mice. Vice versa, Tau species levels were not changed in Cyp46 overexpressing mice with increased neuronal levels of 24OHC. We conclude that the strongly correlative fluxes of 24OHC and Tau from neuronal cells to CSF are likely to be secondary to neurodegeneration and not due to direct interaction between the two factors. We suggest that this high correlation reflects a rapid neurodegeneration of specific neuronal subtypes with simultaneous release of 24OHC and Tau into the CSF. |
format | Online Article Text |
id | pubmed-6137204 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-61372042018-09-21 24S-Hydroxycholesterol Correlates With Tau and Is Increased in Cerebrospinal Fluid in Parkinson's Disease and Corticobasal Syndrome Björkhem, Ingemar Patra, Kalicharan Boxer, Adam L. Svenningsson, Per Front Neurol Neurology 24S-hydroxycholesterol (24OHC) and Tau are produced in neuronal cells and neurodegeneration leads to increased flux of both of them into cerebrospinal fluid (CSF). In the present study, CSF levels of 24OHC and 27S-hydroxycholesterol (27OHC) along with those of Tau, P-Thr(181)-Tau and Aβ(42) were measured in patients with early Parkinson's disease (PD), Corticobasal syndrome (CBS), Corticobasal Degeneration (CBD), and controls. Using mouse models with increased or no formation of Tau protein and increased production of 24OHC, we have also tested the hypothesis that there is a direct association between neuronal turnover of 24OHC and Tau. The levels of 24OHC are increased, at a group level, in patients with PD or CBS. We found significant correlations between levels of 24OHC and Tau or P-Thr(181)-Tau in CSF from patients with PD, CBS or CBD. There were no similar correlations between 24OHC and Aβ(42) in CSF from these patients. The neuronal levels of 24OHC were not altered in Tau knockout or Tau overexpressing mice. Vice versa, Tau species levels were not changed in Cyp46 overexpressing mice with increased neuronal levels of 24OHC. We conclude that the strongly correlative fluxes of 24OHC and Tau from neuronal cells to CSF are likely to be secondary to neurodegeneration and not due to direct interaction between the two factors. We suggest that this high correlation reflects a rapid neurodegeneration of specific neuronal subtypes with simultaneous release of 24OHC and Tau into the CSF. Frontiers Media S.A. 2018-09-07 /pmc/articles/PMC6137204/ /pubmed/30245667 http://dx.doi.org/10.3389/fneur.2018.00756 Text en Copyright © 2018 Björkhem, Patra, Boxer and Svenningsson. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neurology Björkhem, Ingemar Patra, Kalicharan Boxer, Adam L. Svenningsson, Per 24S-Hydroxycholesterol Correlates With Tau and Is Increased in Cerebrospinal Fluid in Parkinson's Disease and Corticobasal Syndrome |
title | 24S-Hydroxycholesterol Correlates With Tau and Is Increased in Cerebrospinal Fluid in Parkinson's Disease and Corticobasal Syndrome |
title_full | 24S-Hydroxycholesterol Correlates With Tau and Is Increased in Cerebrospinal Fluid in Parkinson's Disease and Corticobasal Syndrome |
title_fullStr | 24S-Hydroxycholesterol Correlates With Tau and Is Increased in Cerebrospinal Fluid in Parkinson's Disease and Corticobasal Syndrome |
title_full_unstemmed | 24S-Hydroxycholesterol Correlates With Tau and Is Increased in Cerebrospinal Fluid in Parkinson's Disease and Corticobasal Syndrome |
title_short | 24S-Hydroxycholesterol Correlates With Tau and Is Increased in Cerebrospinal Fluid in Parkinson's Disease and Corticobasal Syndrome |
title_sort | 24s-hydroxycholesterol correlates with tau and is increased in cerebrospinal fluid in parkinson's disease and corticobasal syndrome |
topic | Neurology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6137204/ https://www.ncbi.nlm.nih.gov/pubmed/30245667 http://dx.doi.org/10.3389/fneur.2018.00756 |
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