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Differing associations between Aβ accumulation, hypoperfusion, blood–brain barrier dysfunction and loss of PDGFRB pericyte marker in the precuneus and parietal white matter in Alzheimer's disease

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)103-115
Number of pages13
JournalJournal of Cerebral Blood Flow and Metabolism
Volume38
Issue number1
Early online date2 Jan 2017
DOIs
DateAccepted/In press - 2 Jan 2017
DateE-pub ahead of print - 2 Jan 2017
DatePublished (current) - 1 Jan 2018

Abstract

Recent studies implicate loss of pericytes in hypoperfusion and blood–brain barrier (BBB) leakage in Alzheimer's disease (AD). In this study, we have measured levels of the pericyte marker, platelet-derived growth factor receptor-β (PDGFRB), and fibrinogen (to assess blood–brain barrier leakage), and analyzed their relationship to indicators of microvessel density (von Willebrand factor level), ante-mortem oxygenation (myelin-associated glycoprotein:proteolipid protein-1 ratio and vascular endothelial growth factor level), Aβ level and plaque load, in precuneus and underlying white matter from 49 AD to 37 control brains. There was reduction in PDGFRB and increased fibrinogen in the precuneus in AD. These changes correlated with reduction in oxygenation and with plaque load. In the underlying white matter, increased fibrinogen correlated with reduced oxygenation, but PDGFRB level was unchanged. The level of platelet-derived growth factor-ββ (PDGF-BB), important for pericyte maintenance, was increased in AD but mainly in the insoluble tissue fraction, correlating with insoluble Aβ level. Loss of the PDGFRB within the precuneus in AD is associated with fibrinogen leakage and reduced oxygenation, and related to fibrillar Aβ accumulation. In contrast, fibrinogen leakage and reduced oxygenation of underlying white matter occur independently of loss of PDGFRB, perhaps secondary to reduced transcortical perfusion.

    Research areas

  • Alzheimer's disease, blood–brain barrier, cerebral hypoperfusion, fibrinogen, pericyte

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    Rights statement: This is the final published version of the article (version of record). It first appeared online via Sage at http://journals.sagepub.com/doi/10.1177/0271678X17690761. Please refer to any applicable terms of use of the publisher.

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