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Evaluation of Neurofilament Light Chain as a Biomarker of Neurodegeneration in X-Linked Childhood Cerebral Adrenoleukodystrophy

Cerebral adrenoleukodystrophy (CALD) is a devastating, demyelinating neuroinflammatory manifestation found in up to 40% of young males with an inherited mutation in ABCD1, the causative gene in adrenoleukodystrophy. The search for biomarkers which correlate to CALD disease burden and respond to inte...

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Autores principales: Wang, Hongge, Davison, Matthew D., Kramer, Martin L., Qiu, Weiliang, Gladysheva, Tatiana, Chiang, Ruby M. S., Kayatekin, Can, Nascene, David R., Taghizadeh, Leyla A., King, Carina J., Nolan, Erin E., Gupta, Ashish O., Orchard, Paul J., Lund, Troy C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8909395/
https://www.ncbi.nlm.nih.gov/pubmed/35269535
http://dx.doi.org/10.3390/cells11050913
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author Wang, Hongge
Davison, Matthew D.
Kramer, Martin L.
Qiu, Weiliang
Gladysheva, Tatiana
Chiang, Ruby M. S.
Kayatekin, Can
Nascene, David R.
Taghizadeh, Leyla A.
King, Carina J.
Nolan, Erin E.
Gupta, Ashish O.
Orchard, Paul J.
Lund, Troy C.
author_facet Wang, Hongge
Davison, Matthew D.
Kramer, Martin L.
Qiu, Weiliang
Gladysheva, Tatiana
Chiang, Ruby M. S.
Kayatekin, Can
Nascene, David R.
Taghizadeh, Leyla A.
King, Carina J.
Nolan, Erin E.
Gupta, Ashish O.
Orchard, Paul J.
Lund, Troy C.
author_sort Wang, Hongge
collection PubMed
description Cerebral adrenoleukodystrophy (CALD) is a devastating, demyelinating neuroinflammatory manifestation found in up to 40% of young males with an inherited mutation in ABCD1, the causative gene in adrenoleukodystrophy. The search for biomarkers which correlate to CALD disease burden and respond to intervention has long been sought after. We used the Olink Proximity Extension Assay (Uppsala, Sweden) to explore the cerebral spinal fluid (CSF) of young males with CALD followed by correlative analysis with plasma. Using the Target 96 Neuro Exploratory panel, we found that, of the five proteins significantly increased in CSF, only neurofilament light chain (NfL) showed a significant correlation between CSF and plasma levels. Young males with CALD had a 11.3-fold increase in plasma NfL compared with controls. Importantly, 9 of 11 young males with CALD who underwent HCT showed a mean decrease in plasma NfL of 50% at 1 year after HCT compared with pre-HCT levels. In conclusion, plasma NfL could be a great value in determining outcomes in CALD and should be scrutinized in future studies in patients prior to CALD development and after therapeutic intervention.
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spelling pubmed-89093952022-03-11 Evaluation of Neurofilament Light Chain as a Biomarker of Neurodegeneration in X-Linked Childhood Cerebral Adrenoleukodystrophy Wang, Hongge Davison, Matthew D. Kramer, Martin L. Qiu, Weiliang Gladysheva, Tatiana Chiang, Ruby M. S. Kayatekin, Can Nascene, David R. Taghizadeh, Leyla A. King, Carina J. Nolan, Erin E. Gupta, Ashish O. Orchard, Paul J. Lund, Troy C. Cells Article Cerebral adrenoleukodystrophy (CALD) is a devastating, demyelinating neuroinflammatory manifestation found in up to 40% of young males with an inherited mutation in ABCD1, the causative gene in adrenoleukodystrophy. The search for biomarkers which correlate to CALD disease burden and respond to intervention has long been sought after. We used the Olink Proximity Extension Assay (Uppsala, Sweden) to explore the cerebral spinal fluid (CSF) of young males with CALD followed by correlative analysis with plasma. Using the Target 96 Neuro Exploratory panel, we found that, of the five proteins significantly increased in CSF, only neurofilament light chain (NfL) showed a significant correlation between CSF and plasma levels. Young males with CALD had a 11.3-fold increase in plasma NfL compared with controls. Importantly, 9 of 11 young males with CALD who underwent HCT showed a mean decrease in plasma NfL of 50% at 1 year after HCT compared with pre-HCT levels. In conclusion, plasma NfL could be a great value in determining outcomes in CALD and should be scrutinized in future studies in patients prior to CALD development and after therapeutic intervention. MDPI 2022-03-07 /pmc/articles/PMC8909395/ /pubmed/35269535 http://dx.doi.org/10.3390/cells11050913 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wang, Hongge
Davison, Matthew D.
Kramer, Martin L.
Qiu, Weiliang
Gladysheva, Tatiana
Chiang, Ruby M. S.
Kayatekin, Can
Nascene, David R.
Taghizadeh, Leyla A.
King, Carina J.
Nolan, Erin E.
Gupta, Ashish O.
Orchard, Paul J.
Lund, Troy C.
Evaluation of Neurofilament Light Chain as a Biomarker of Neurodegeneration in X-Linked Childhood Cerebral Adrenoleukodystrophy
title Evaluation of Neurofilament Light Chain as a Biomarker of Neurodegeneration in X-Linked Childhood Cerebral Adrenoleukodystrophy
title_full Evaluation of Neurofilament Light Chain as a Biomarker of Neurodegeneration in X-Linked Childhood Cerebral Adrenoleukodystrophy
title_fullStr Evaluation of Neurofilament Light Chain as a Biomarker of Neurodegeneration in X-Linked Childhood Cerebral Adrenoleukodystrophy
title_full_unstemmed Evaluation of Neurofilament Light Chain as a Biomarker of Neurodegeneration in X-Linked Childhood Cerebral Adrenoleukodystrophy
title_short Evaluation of Neurofilament Light Chain as a Biomarker of Neurodegeneration in X-Linked Childhood Cerebral Adrenoleukodystrophy
title_sort evaluation of neurofilament light chain as a biomarker of neurodegeneration in x-linked childhood cerebral adrenoleukodystrophy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8909395/
https://www.ncbi.nlm.nih.gov/pubmed/35269535
http://dx.doi.org/10.3390/cells11050913
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