Annexin A5 prevents amyloid-β-induced toxicity in choroid plexus : implication for Alzheimer's disease
Bartolome, Fernando (Instituto de Investigación Sanitaria Hospital 12 de Octubre (i+12))
Krzyzanowska, Agnieszka (Instituto de Investigación Sanitaria Hospital 12 de Octubre (i+12))
de la Cueva, Macarena (Instituto de Investigación Sanitaria Hospital 12 de Octubre (i+12))
Pascual, Consuelo (Instituto de Investigación Sanitaria Hospital 12 de Octubre (i+12))
Antequera, Desiree (Instituto de Investigación Sanitaria Hospital 12 de Octubre (i+12))
Spuch, Carlos (Centro de Investigación Biomédica en Red de Salud Mental)
Villarejo-Galende, Alberto (Hospital Universitario 12 de Octubre (Madrid))
Rábano, Alberto (Fundación Centro de Investigación de Enfermedades Neurológicas (CIEN))
Fortea, Juan (Institut d'Investigació Biomèdica Sant Pau)
Alcolea, Daniel (Institut d'Investigació Biomèdica Sant Pau)
Lleó, Alberto (Institut d'Investigació Biomèdica Sant Pau)
Ferrer, Isidro (Universitat de Barcelona)
Hardy, John (UCL Institute of Neurology (Regne Unit))
Abramov, Andrey Y. (UCL Institute of Neurology (Regne Unit))
Carro, Eva (Instituto de Investigación Sanitaria Hospital 12 de Octubre (i+12))
Universitat Autònoma de Barcelona

Fecha:	2020
Resumen:	In Alzheimer's disease (AD) amyloid-β (Aβ) deposits may cause impairments in choroid plexus, a specialised brain structure which forms the blood-cerebrospinal fluid (CSF) barrier. We previously carried out a mass proteomic-based study in choroid plexus from AD patients and we found several differentially regulated proteins compared with healthy subjects. One of these proteins, annexin A5, was previously demonstrated implicated in blocking Aβ-induced cytotoxicity in neuronal cell cultures. Here, we investigated the effects of annexin A5 on Aβ toxicity in choroid plexus. We used choroid plexus tissue samples and CSF from mild cognitive impairment (MCI) and AD patients to analyse Aβ accumulation, cell death and annexin A5 levels compared with control subjects. Choroid plexus cell cultures from rats were used to analyse annexin A5 effects on Aβ-induced cytotoxicity. AD choroid plexus exhibited progressive reduction of annexin A5 levels along with progressive increased Aβ accumulation and cell death as disease stage was higher. On the other hand, annexin A5 levels in CSF from patients were found progressively increased as the disease stage increased in severity. In choroid plexus primary cultures, Aβ administration reduced endogenous annexin A5 levels in a time-course dependent manner and simultaneously increased annexin A5 levels in extracellular medium. Annexin A5 addition to choroid plexus cell cultures restored the Aβ-induced impairments on autophagy flux and apoptosis in a calcium-dependent manner. We propose that annexin A5 would exert a protective role in choroid plexus and this protection is lost as Aβ accumulates with the disease progression. Then, brain protection against further toxic insults would be jeopardised.
Ayudas:	Instituto de Salud Carlos III PI18/00118 Instituto de Salud Carlos III FIS2015/00780 Instituto de Salud Carlos III PI2016/01
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Cell death in the nervous system ; Bioenergetics ; Neurological disorders
Publicado en:	Scientific reports, Vol. 10 (june 2020) , ISSN 2045-2322

DOI: 10.1038/s41598-020-66177-5
PMID: 32523019

15 p, 5.0 MB

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Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut de Recerca Sant Pau
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