title: Cross-talk between Aβ and endothelial SSAO/VAP-1 accelerates vascular damage and Aβ aggregation related to CAA-AD.
abstract: 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 in vitro, 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 in vitro. 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.
authors.affiliation: Institut de Neurociències i Departament de Bioquímica i Biologia Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain. Electronic address: montserrat.sole@uab.cat.
authors.forename: Montse
authors.initials: M
authors.lastname: Solé
authors.affiliation: Institut de Neurociències i Departament de Bioquímica i Biologia Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
authors.forename: Alfredo J
authors.initials: AJ
authors.lastname: Miñano-Molina
authors.affiliation: Institut de Neurociències i Departament de Bioquímica i Biologia Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Unzeta
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D006631:Amine Oxidase (Copper-Containing) / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D017209:Apoptosis; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D016657:Cerebral Amyloid Angiopathy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D015870:Gene Expression; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D058990:Molecular Targeted Therapy; D018384:Oxidative Stress
chemical_list: D016229:Amyloid beta-Peptides; D015815:Cell Adhesion Molecules; D017127:Glycation End Products, Advanced; C076668:AOC3 protein, human; D006631:Amine Oxidase (Copper-Containing)
keywords: Alzheimer's disease; Amyloid-beta aggregation; Cerebral amyloid angiopathy (CAA); Semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 (SSAO/VAP-1); Vascular damage