Aβ42 production in brain capillary endothelial cells after oxygen and glucose deprivation

Alessandra Bulbarelli, Elena Lonati, Anna Brambilla, Antonina Orlando, Emanuela Cazzaniga, Fabrizio Piazza, Carlo Ferrarese, Massimo Masserini, Giulio Sancini

Research output: Contribution to journalArticlepeer-review

Abstract

Although the diverse triggers of AD are still under debate, the hypothesis of the contribution of cerebrovascular deficiencies has emerged in recent years. Cerebrovascular dysfunction may precede cognitive decline and onset of neurodegeneration. Indeed, the toxic Aβ 42 aggregates constituting senile plaques, one of AD hallmarks, is often detected as amorphous material or fine fibrils in the brain capillary of AD patients. Aβ 42 causing cerebral microangiopathy might originate either from the circulating blood, the vessel wall itself or the brain parenchyma. In the present investigation we show, for the first time, that in rat brain capillary endothelial cells (RBE4), in vitro oxygen glucose deprivation treatment elicits 250% of Aβ 42 peptide production increase through a mechanism that involves the hypoxia inducible factor-1-mediated β-secretase (BACE1) up-regulation. Furthermore, we observed a time dependent increase of amyloid protein precursor (AβPP) gene and protein expression, confirming previous reports which established the existence of AβPP in the cerebrovascular domain.Our experimental evidences point out that ischemic events may directly contribute in brain capillary endothelial cells to the enhancement of the amyloidogenic metabolism, leading to intracellular deposition of Aβ 42. This events may contribute to the impairment of Aβ brain clearance and AD related blood brain barrier dysfunctions.

Original languageEnglish
Pages (from-to)415-422
Number of pages8
JournalMolecular and Cellular Neuroscience
Volume49
Issue number4
DOIs
Publication statusPublished - Apr 2012

Keywords

  • Alzheimer's disease
  • Amyloid-β 1-42
  • Amyloid-β protein precursor
  • Blood brain barrier
  • Brain ischemia-anoxia
  • HIF-1alpha protein

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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