Targeting Beta-Amyloid at the CSF: A New Therapeutic Strategy in Alzheimer’s Disease

Although immunotherapies against the amyloid-b (Ab) peptide tried so date failed to prove sufficient clinical benefit, Ab still remains the main target in Alzheimer’s disease (AD). This article aims to show the rationale of a new therapeutic strategy: clearing Ab from the CSF continuously (the “CSF-...

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Autores: Menéndez González, Manuel, Padilla Zambrano, Huber S., Álvarez, Gabriel, Capetillo González de Zárate, Estíbaliz, Tomás Zapico, Cristina, Costa García, Agustín
Tipo de recurso: artículo
Fecha de publicación:2018
País:España
Institución:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/70748
Acceso en línea:http://hdl.handle.net/10810/70748
Access Level:acceso abierto
Palabra clave:Alzheimer disease
amyloid beta-peptides
cerebrospinal fluid
immunotherapy
CSF sink hypothesis
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spelling Targeting Beta-Amyloid at the CSF: A New Therapeutic Strategy in Alzheimer’s DiseaseMenéndez González, ManuelPadilla Zambrano, Huber S.Álvarez, GabrielCapetillo González de Zárate, EstíbalizTomás Zapico, CristinaCosta García, AgustínAlzheimer diseaseamyloid beta-peptidescerebrospinal fluidimmunotherapyCSF sink hypothesisAlthough immunotherapies against the amyloid-b (Ab) peptide tried so date failed to prove sufficient clinical benefit, Ab still remains the main target in Alzheimer’s disease (AD). This article aims to show the rationale of a new therapeutic strategy: clearing Ab from the CSF continuously (the “CSF-sink” therapeutic strategy). First, we describe the physiologic mechanisms of Ab clearance and the resulting AD pathology when these mechanisms are altered. Then, we review the experiences with peripheral Ab-immunotherapy and discuss the related hypothesis of the mechanism of action of “peripheral sink.” We also present Ab immunotherapies acting on the CNS directly. Finally, we introduce alternative methods of removing Ab including the “CSF-sink” therapeutic strategy. As soluble peptides are in constant equilibrium between the ISF and the CSF, altering the levels of Ab oligomers in the CSF would also alter the levels of such proteins in the brain parenchyma. We conclude that interventions based in a “CSF-sink” of Ab will probably produce a steady clearance of Ab in the ISF and therefore it may represent a new therapeutic strategy in AD.Frontiers Media202420242018info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10810/70748reponame:Addi. Archivo Digital para la Docencia y la Investigacióninstname:Universidad del País VascoIngléshttps://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2018.00100/fullinfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/© 2018 Menendez-Gonzalez, Padilla-Zambrano, Alvarez, Capetillo-Zarate, Tomas-Zapico and Costa. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).oai:addi.ehu.eus:10810/707482026-06-18T09:23:17Z
dc.title.none.fl_str_mv Targeting Beta-Amyloid at the CSF: A New Therapeutic Strategy in Alzheimer’s Disease
title Targeting Beta-Amyloid at the CSF: A New Therapeutic Strategy in Alzheimer’s Disease
spellingShingle Targeting Beta-Amyloid at the CSF: A New Therapeutic Strategy in Alzheimer’s Disease
Menéndez González, Manuel
Alzheimer disease
amyloid beta-peptides
cerebrospinal fluid
immunotherapy
CSF sink hypothesis
title_short Targeting Beta-Amyloid at the CSF: A New Therapeutic Strategy in Alzheimer’s Disease
title_full Targeting Beta-Amyloid at the CSF: A New Therapeutic Strategy in Alzheimer’s Disease
title_fullStr Targeting Beta-Amyloid at the CSF: A New Therapeutic Strategy in Alzheimer’s Disease
title_full_unstemmed Targeting Beta-Amyloid at the CSF: A New Therapeutic Strategy in Alzheimer’s Disease
title_sort Targeting Beta-Amyloid at the CSF: A New Therapeutic Strategy in Alzheimer’s Disease
dc.creator.none.fl_str_mv Menéndez González, Manuel
Padilla Zambrano, Huber S.
Álvarez, Gabriel
Capetillo González de Zárate, Estíbaliz
Tomás Zapico, Cristina
Costa García, Agustín
author Menéndez González, Manuel
author_facet Menéndez González, Manuel
Padilla Zambrano, Huber S.
Álvarez, Gabriel
Capetillo González de Zárate, Estíbaliz
Tomás Zapico, Cristina
Costa García, Agustín
author_role author
author2 Padilla Zambrano, Huber S.
Álvarez, Gabriel
Capetillo González de Zárate, Estíbaliz
Tomás Zapico, Cristina
Costa García, Agustín
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Alzheimer disease
amyloid beta-peptides
cerebrospinal fluid
immunotherapy
CSF sink hypothesis
topic Alzheimer disease
amyloid beta-peptides
cerebrospinal fluid
immunotherapy
CSF sink hypothesis
description Although immunotherapies against the amyloid-b (Ab) peptide tried so date failed to prove sufficient clinical benefit, Ab still remains the main target in Alzheimer’s disease (AD). This article aims to show the rationale of a new therapeutic strategy: clearing Ab from the CSF continuously (the “CSF-sink” therapeutic strategy). First, we describe the physiologic mechanisms of Ab clearance and the resulting AD pathology when these mechanisms are altered. Then, we review the experiences with peripheral Ab-immunotherapy and discuss the related hypothesis of the mechanism of action of “peripheral sink.” We also present Ab immunotherapies acting on the CNS directly. Finally, we introduce alternative methods of removing Ab including the “CSF-sink” therapeutic strategy. As soluble peptides are in constant equilibrium between the ISF and the CSF, altering the levels of Ab oligomers in the CSF would also alter the levels of such proteins in the brain parenchyma. We conclude that interventions based in a “CSF-sink” of Ab will probably produce a steady clearance of Ab in the ISF and therefore it may represent a new therapeutic strategy in AD.
publishDate 2018
dc.date.none.fl_str_mv 2018
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10810/70748
url http://hdl.handle.net/10810/70748
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2018.00100/full
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:Addi. Archivo Digital para la Docencia y la Investigación
instname:Universidad del País Vasco
instname_str Universidad del País Vasco
reponame_str Addi. Archivo Digital para la Docencia y la Investigación
collection Addi. Archivo Digital para la Docencia y la Investigación
repository.name.fl_str_mv
repository.mail.fl_str_mv
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