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

Alzheimers Res Ther. 2019 Sep 14;11(1):81. doi: 10.1186/s13195-019-0534-8.

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.

Keywords: Alzheimer’s disease; CSF; CSF albumin; Cerebrospinal fluid; PDGFRβ; Platelet-derived growth factor receptor β.

MeSH terms

  • Aged
  • Albumins / cerebrospinal fluid
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / pathology*
  • Biomarkers / cerebrospinal fluid
  • Blood-Brain Barrier / pathology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pericytes / pathology*
  • Receptor, Platelet-Derived Growth Factor beta / cerebrospinal fluid

Substances

  • Albumins
  • Biomarkers
  • Receptor, Platelet-Derived Growth Factor beta