A cross-talk between Aβ and endothelial SSAO/VAP-1 accelerates vascular damage and Aβ aggregation related to CAA-AD

Montse Solé, Alfredo J. Miñano-Molina, Mercedes Unzeta

Research output: Contribution to journalArticleResearchpeer-review

14 Citations (Scopus)

Abstract

© 2015 Elsevier Inc. An association between semicarbazide-sensitive amine oxidase (SSAO) and cerebral amyloid angiopathy (CAA) related to Alzheimer's disease (AD) has been largely postulated. Increased SSAO activity and expression have been detected in cerebrovascular tissue and plasma of AD patients, colocalizing with cerebrovascular amyloid-beta (Aβ) deposits. As an enzyme, SSAO metabolizes primary amines generating hydrogen peroxide, ammonia, and aldehydes. The ability of these products to generate oxidative stress, to enhance the advanced glycation end-product generation, to promote the Aβ aggregation invitro, and to induce apoptosis supports its role in CAA-related vascular pathology. However, whether the SSAO increase constitutes a cause or it is a consequence of the pathologic process has not been elucidated so far. To set up the nature of this relationship, vascular cell models expressing SSAO were treated with different Aβ forms, simulating the CAA conditions invitro. It was found that the presence of the vasculotropic Dutch-mutated Aβ1-40 increases (Aβ1-40 D) the SSAO-dependent toxicity, which is accompanied by an increase of SSAO protein availability in endothelial cell membranes. In addition, SSAO enhances Aβ1-40 D and Aβ1-42 deposition on vascular cells by both activity-dependent and -independent mechanisms. Thus, we provide evidences indicating that Aβ itself could be one of the factors inducing SSAO increase in AD, enhancing its toxic effect, and inducing the vascular dysfunction and, in turn, that SSAO stimulates Aβ deposition on the vascular walls, thereby contributing to the CAA-AD progression. Therefore, molecules inhibiting SSAO could provide an alternative treatment for preventing/delaying the progress of CAA-AD-associated vasculopathy.
Original languageEnglish
Pages (from-to)762-775
JournalNeurobiology of Aging
Volume36
Issue number2
DOIs
Publication statusPublished - 1 Jan 2015

Keywords

  • Alzheimer's disease
  • Amyloid-beta aggregation
  • Cerebral amyloid angiopathy (CAA)
  • Semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 (SSAO/VAP-1)
  • Vascular damage

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