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01.12.2019 | Research | Ausgabe 1/2019 Open Access

Alzheimer's Research & Therapy 1/2019

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

Zeitschrift:
Alzheimer's Research & Therapy > Ausgabe 1/2019
Autoren:
J. S. Miners, P. G. Kehoe, S. Love, H. Zetterberg, K. Blennow
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s13195-019-0534-8) contains supplementary material, which is available to authorized users.
Z. Zetterberg and K. Blennow contributed equally to this work.
Zetterberg Z and Blennow K shared last authorship.

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Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Abstract

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.
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