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Choroid plexus dysfunction impairs beta-amyloid clearance in a triple transgenic mouse model of Alzheimer's disease
González-Marrero, Ibrahim (Universidad de La Laguna. Departamento de Anatomía Humana)
Giménez Llort, Lydia (Universitat Autònoma de Barcelona. Institut de Neurociències)
Johanson, Conrad E. (Alpert Medical School at Brown University. Department of Neurosurgery)
Carmona-Calero, Emilia María (Universidad de La Laguna. Departamento de Anatomía Humana)
Castañeyra-Ruiz, Leandro (Universidad de La Laguna. Departamento de Anatomía Humana)
Brito-Armas, José Miguel (Universidad de La Laguna. Departamento de Psicología)
Castañeyra-Perdomo, Agustín (Universidad de La Laguna. Departamento de Anatomía Humana)
Castro-Fuentes, Rafael (Universidad de La Laguna. Departamento de Psicología)
Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal

Date: 2015
Abstract: Compromised secretory function of choroid plexus (CP) and defective cerebrospinal fluid (CSF) production, along with accumulation of beta-amyloid (Aβ) peptides at the blood-CSF barrier (BCSFB), contribute to complications of Alzheimer's disease (AD). The AD triple transgenic mouse model (3xTg-AD) at 16 month-old mimics critical hallmarks of the human disease: β-amyloid (Aβ) plaques and neurofibrillary tangles (NFT) with a temporal- and regional- specific profile. Currently, little is known about transport and metabolic responses by CP to the disrupted homeostasis of CNS Aβ in AD. This study analyzed the effects of highly-expressed AD-linked human transgenes (APP, PS1 and tau) on lateral ventricle CP function. Confocal imaging and immunohistochemistry revealed an increase only of Aβ42 isoform in epithelial cytosol and in stroma surrounding choroidal capillaries; this buildup may reflect insufficient clearance transport from CSF to blood. Still, there was increased expression, presumably compensatory, of the choroidal Aβ transporters: the low density lipoprotein receptor-related protein 1 (LRP1) and the receptor for advanced glycation end product (RAGE). A thickening of the epithelial basal membrane and greater collagen-IV deposition occurred around capillaries in CP, probably curtailing solute exchanges. Moreover, there was attenuated expression of epithelial aquaporin-1 and transthyretin (TTR) protein compared to Non-Tg mice. Collectively these findings indicate CP dysfunction hypothetically linked to increasing Aβ burden resulting in less efficient ion transport, concurrently with reduced production of CSF (less sink action on brain Aβ) and diminished secretion of TTR (less neuroprotection against cortical Aβ toxicity). The putative effects of a disabled CP-CSF system on CNS functions are discussed in the context of AD.
Note: Número d'acord de subvenció ISCIII/PI10-00283
Rights: 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. Creative Commons
Language: Anglès.
Document: article ; recerca ; publishedVersion
Subject: Alzheimer disease ; 3xTg-AD mice ; Choroid plexus ; Dysfunction ; Amyloid-β ; Collagen-IV ; Transthyretin ; Aquaporin-1
Published in: Frontiers in Cellular Neuroscience, Vol. 9 (February 2015) , art. 17, ISSN 1662-5102

PMID: 25705176
DOI: 10.3389/fncel.2015.00017


10 p, 1.8 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (scientific output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles

 Record created 2018-01-31, last modified 2019-03-23



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