Cargando…
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...
Autores principales: | , , , , |
---|---|
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 |
_version_ | 1783451478410657792 |
---|---|
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. |
format | Online Article Text |
id | pubmed-6745071 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT minersjs csfevidenceofpericytedamageinalzheimersdiseaseisassociatedwithmarkersofbloodbrainbarrierdysfunctionanddiseasepathology AT kehoepg csfevidenceofpericytedamageinalzheimersdiseaseisassociatedwithmarkersofbloodbrainbarrierdysfunctionanddiseasepathology AT loves csfevidenceofpericytedamageinalzheimersdiseaseisassociatedwithmarkersofbloodbrainbarrierdysfunctionanddiseasepathology AT zetterbergh csfevidenceofpericytedamageinalzheimersdiseaseisassociatedwithmarkersofbloodbrainbarrierdysfunctionanddiseasepathology AT blennowk csfevidenceofpericytedamageinalzheimersdiseaseisassociatedwithmarkersofbloodbrainbarrierdysfunctionanddiseasepathology |