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CSF evidence of pericyte damage in Alzheimer’s disease is associated with markers of blood-brain barrier dysfunction and disease pathology

BACKGROUND: We aimed to assess the relationship between levels of a cerebrospinal fluid (CSF) marker of pericyte damage, soluble platelet-derived growth factor receptor β (sPDGFRβ) and CSF markers of blood-brain barrier (BBB) integrity (CSF albumin and CSF/serum albumin ratio) and disease pathology...

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Autores principales: Miners, J. S., Kehoe, P. G., Love, S., Zetterberg, H., Blennow, K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6745071/
https://www.ncbi.nlm.nih.gov/pubmed/31521199
http://dx.doi.org/10.1186/s13195-019-0534-8
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author Miners, J. S.
Kehoe, P. G.
Love, S.
Zetterberg, H.
Blennow, K.
author_facet Miners, J. S.
Kehoe, P. G.
Love, S.
Zetterberg, H.
Blennow, K.
author_sort Miners, J. S.
collection PubMed
description BACKGROUND: We aimed to assess the relationship between levels of a cerebrospinal fluid (CSF) marker of pericyte damage, soluble platelet-derived growth factor receptor β (sPDGFRβ) and CSF markers of blood-brain barrier (BBB) integrity (CSF albumin and CSF/serum albumin ratio) and disease pathology (reduced CSF Aβ42 and elevated CSF total and phosphorylated tau) in Alzheimer’s disease (AD). METHODS: sPDGFRβ and albumin were measured by sandwich ELISA in ante-mortem CSF from 39 AD and 39 age-matched controls that were grouped according to their biomarker profile (i.e. AD cases t-tau > 400 pg/mL, p-tau > 60 pg/mL and Aβ42 < 550 pg/mL). sPDGFRβ was also measured in matched serum and CSF samples (n = 23) in a separate neurologically normal group for which the CSF/serum albumin ratio had been determined. RESULTS: CSF sPDGFRβ level was significantly increased in AD (p = 0.0038) and correlated positively with albumin (r = 0.45, p = 0.007), total tau (r = 0.50, p = 0.0017) and phosphorylated tau (r = 0.41, p = 0.013) in AD but not in controls. CSF sPDGFRβ did not correlate with Aβ42. Serum and CSF sPDGFRβ were positively correlated (r = 0.547, p = 0.0085) in the independent neurologically normal CSF/serum matched samples. CONCLUSIONS: We provide further evidence of an association between pericyte injury and BBB breakdown in AD and novel evidence that a CSF marker of pericyte injury is related to the severity of AD pathology. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13195-019-0534-8) contains supplementary material, which is available to authorized users.
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spelling pubmed-67450712019-09-18 CSF evidence of pericyte damage in Alzheimer’s disease is associated with markers of blood-brain barrier dysfunction and disease pathology Miners, J. S. Kehoe, P. G. Love, S. Zetterberg, H. Blennow, K. Alzheimers Res Ther Research BACKGROUND: We aimed to assess the relationship between levels of a cerebrospinal fluid (CSF) marker of pericyte damage, soluble platelet-derived growth factor receptor β (sPDGFRβ) and CSF markers of blood-brain barrier (BBB) integrity (CSF albumin and CSF/serum albumin ratio) and disease pathology (reduced CSF Aβ42 and elevated CSF total and phosphorylated tau) in Alzheimer’s disease (AD). METHODS: sPDGFRβ and albumin were measured by sandwich ELISA in ante-mortem CSF from 39 AD and 39 age-matched controls that were grouped according to their biomarker profile (i.e. AD cases t-tau > 400 pg/mL, p-tau > 60 pg/mL and Aβ42 < 550 pg/mL). sPDGFRβ was also measured in matched serum and CSF samples (n = 23) in a separate neurologically normal group for which the CSF/serum albumin ratio had been determined. RESULTS: CSF sPDGFRβ level was significantly increased in AD (p = 0.0038) and correlated positively with albumin (r = 0.45, p = 0.007), total tau (r = 0.50, p = 0.0017) and phosphorylated tau (r = 0.41, p = 0.013) in AD but not in controls. CSF sPDGFRβ did not correlate with Aβ42. Serum and CSF sPDGFRβ were positively correlated (r = 0.547, p = 0.0085) in the independent neurologically normal CSF/serum matched samples. CONCLUSIONS: We provide further evidence of an association between pericyte injury and BBB breakdown in AD and novel evidence that a CSF marker of pericyte injury is related to the severity of AD pathology. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13195-019-0534-8) contains supplementary material, which is available to authorized users. BioMed Central 2019-09-14 /pmc/articles/PMC6745071/ /pubmed/31521199 http://dx.doi.org/10.1186/s13195-019-0534-8 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Miners, J. S.
Kehoe, P. G.
Love, S.
Zetterberg, H.
Blennow, K.
CSF evidence of pericyte damage in Alzheimer’s disease is associated with markers of blood-brain barrier dysfunction and disease pathology
title CSF evidence of pericyte damage in Alzheimer’s disease is associated with markers of blood-brain barrier dysfunction and disease pathology
title_full CSF evidence of pericyte damage in Alzheimer’s disease is associated with markers of blood-brain barrier dysfunction and disease pathology
title_fullStr CSF evidence of pericyte damage in Alzheimer’s disease is associated with markers of blood-brain barrier dysfunction and disease pathology
title_full_unstemmed CSF evidence of pericyte damage in Alzheimer’s disease is associated with markers of blood-brain barrier dysfunction and disease pathology
title_short CSF evidence of pericyte damage in Alzheimer’s disease is associated with markers of blood-brain barrier dysfunction and disease pathology
title_sort csf evidence of pericyte damage in alzheimer’s disease is associated with markers of blood-brain barrier dysfunction and disease pathology
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6745071/
https://www.ncbi.nlm.nih.gov/pubmed/31521199
http://dx.doi.org/10.1186/s13195-019-0534-8
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