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-...
| Authors: | ; ; ; ; ; |
|---|---|
| Format: | Article |
| Publication date: | 2018 |
| Country: | España |
| Institution: | Universidad del País Vasco |
| Repository: | Addi. Archivo Digital para la Docencia y la Investigación |
| OAI Identifier: | oai:addi.ehu.eus:10810/70748 |
| Online Access: | http://hdl.handle.net/10810/70748 |
| Access Level: | Open access |
| Keyword: | Alzheimer disease amyloid beta-peptides cerebrospinal fluid immunotherapy CSF sink hypothesis |
| _version_ | 1878742376061599744 |
|---|---|
| author | Menéndez González, Manuel |
| 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 |
| author_browse | Capetillo González de Zárate, Estíbaliz Costa García, Agustín Menéndez González, Manuel Padilla Zambrano, Huber S. Tomás Zapico, Cristina Álvarez, Gabriel |
| 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 |
| collection | Addi. Archivo Digital para la Docencia y la Investigación |
| 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_f4cd00d7c0bd0e4eaf34fbe89c34b2fb |
| institution | Universidad del País Vasco |
| instname_str | Universidad del País Vasco |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:addi.ehu.eus:10810/70748 |
| publishDate | 2018 |
| publishDateSort | 2018 |
| publisher | Frontiers Media |
| publisherStr | Frontiers Media |
| reponame_str | Addi. Archivo Digital para la Docencia y la Investigación |
| spelling | Targeting Beta-Amyloid at the CSF: A New Therapeutic Strategy in Alzheimer’s Disease Menéndez González, Manuel Padilla Zambrano, Huber S. Álvarez, Gabriel Capetillo González de Zárate, Estíbaliz Tomás Zapico, Cristina Costa García, Agustín Alzheimer disease amyloid beta-peptides cerebrospinal fluid immunotherapy CSF sink hypothesis 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. Frontiers Media http://hdl.handle.net/10810/70748 |
| 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 | 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_short | 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 |
| topic | Alzheimer disease amyloid beta-peptides cerebrospinal fluid immunotherapy CSF sink hypothesis |
| topic_facet | Alzheimer disease amyloid beta-peptides cerebrospinal fluid immunotherapy CSF sink hypothesis |
| url | http://hdl.handle.net/10810/70748 |