In situ structural characterization of early amyloid aggregates in Alzheimer's disease transgenic mice and Octodon degus

Amyloid plaques composed of Aβ amyloid peptides and neurofibrillary tangles are a pathological hallmark of Alzheimer's disease. In situ identification of early-stage amyloid aggregates in Alzheimer's disease is relevant for their importance as potential targets for effective drugs. Synchro...

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Autores: Benseny Cases, Núria|||0000-0003-4603-6829, Álvarez Marimon, Elena|||0000-0001-8571-9521, Aso, Ester|||0000-0003-1836-1747, Carmona, Margarita|||0000-0002-9275-9000, Klementieva, Oxana|||0000-0003-1782-050X, Appelhans, Dietmar|||0000-0003-4611-8963, Ferrer, Isidro|||0000-0001-9888-8754, Cladera i Cerdà, Josep|||0000-0002-1724-3477
Formato: artículo
Fecha de publicación:2020
País:España
Recursos:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:252533
Acesso em linha:https://ddd.uab.cat/record/252533
https://dx.doi.org/urn:doi:10.1038/s41598-020-62708-2
Access Level:acceso abierto
Palavra-chave:Biochemistry
Biophysics
Structural biology
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spelling In situ structural characterization of early amyloid aggregates in Alzheimer's disease transgenic mice and Octodon degusBenseny Cases, Núria|||0000-0003-4603-6829Álvarez Marimon, Elena|||0000-0001-8571-9521Aso, Ester|||0000-0003-1836-1747Carmona, Margarita|||0000-0002-9275-9000Klementieva, Oxana|||0000-0003-1782-050XAppelhans, Dietmar|||0000-0003-4611-8963Ferrer, Isidro|||0000-0001-9888-8754Cladera i Cerdà, Josep|||0000-0002-1724-3477BiochemistryBiophysicsStructural biologyAmyloid plaques composed of Aβ amyloid peptides and neurofibrillary tangles are a pathological hallmark of Alzheimer's disease. In situ identification of early-stage amyloid aggregates in Alzheimer's disease is relevant for their importance as potential targets for effective drugs. Synchrotron-based infrared imaging is here used to identify early-stage oligomeric/granular aggregated amyloid species in situ in the brain of APP/PS1 transgenic mice and Octodon degus for the first time. Also, APP/PS1 mice show fibrillary aggregates at 6 and 12 months whereas very little formation of fibrils is found in aged Octodon degus. Finally, significant decreased burden of early-stage aggregates and fibrillary aggregates is obtained following treatment with G4-His-Mal dendrimers (a neurodegenerative protector) in 6-month-old APP/PS1 mice, thus demonstrating putative therapeutic properties of G4-His-Mal dendrimers in AD models. Identification, localization, and characterization using infrared imaging of these non-fibrillary species in the cerebral cortex at early stages of AD progression in transgenic mice point to their relevance as putative pharmacological targets. No less important, early detection of these structures may be useful in the search for markers for non-invasive diagnostic techniques. 22020-01-0120202020-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/252533https://dx.doi.org/urn:doi:10.1038/s41598-020-62708-2reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengMinisterio de Ciencia, Innovación y Universidades https://doi.org/10.13039/100014440 SAF2017-844-Ropen accesshttp://purl.org/coar/access_right/c_abf2Aquest 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.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2525332026-06-06T12:50:31Z
dc.title.none.fl_str_mv In situ structural characterization of early amyloid aggregates in Alzheimer's disease transgenic mice and Octodon degus
title In situ structural characterization of early amyloid aggregates in Alzheimer's disease transgenic mice and Octodon degus
spellingShingle In situ structural characterization of early amyloid aggregates in Alzheimer's disease transgenic mice and Octodon degus
Benseny Cases, Núria|||0000-0003-4603-6829
Biochemistry
Biophysics
Structural biology
title_short In situ structural characterization of early amyloid aggregates in Alzheimer's disease transgenic mice and Octodon degus
title_full In situ structural characterization of early amyloid aggregates in Alzheimer's disease transgenic mice and Octodon degus
title_fullStr In situ structural characterization of early amyloid aggregates in Alzheimer's disease transgenic mice and Octodon degus
title_full_unstemmed In situ structural characterization of early amyloid aggregates in Alzheimer's disease transgenic mice and Octodon degus
title_sort In situ structural characterization of early amyloid aggregates in Alzheimer's disease transgenic mice and Octodon degus
dc.creator.none.fl_str_mv Benseny Cases, Núria|||0000-0003-4603-6829
Álvarez Marimon, Elena|||0000-0001-8571-9521
Aso, Ester|||0000-0003-1836-1747
Carmona, Margarita|||0000-0002-9275-9000
Klementieva, Oxana|||0000-0003-1782-050X
Appelhans, Dietmar|||0000-0003-4611-8963
Ferrer, Isidro|||0000-0001-9888-8754
Cladera i Cerdà, Josep|||0000-0002-1724-3477
author Benseny Cases, Núria|||0000-0003-4603-6829
author_facet Benseny Cases, Núria|||0000-0003-4603-6829
Álvarez Marimon, Elena|||0000-0001-8571-9521
Aso, Ester|||0000-0003-1836-1747
Carmona, Margarita|||0000-0002-9275-9000
Klementieva, Oxana|||0000-0003-1782-050X
Appelhans, Dietmar|||0000-0003-4611-8963
Ferrer, Isidro|||0000-0001-9888-8754
Cladera i Cerdà, Josep|||0000-0002-1724-3477
author_role author
author2 Álvarez Marimon, Elena|||0000-0001-8571-9521
Aso, Ester|||0000-0003-1836-1747
Carmona, Margarita|||0000-0002-9275-9000
Klementieva, Oxana|||0000-0003-1782-050X
Appelhans, Dietmar|||0000-0003-4611-8963
Ferrer, Isidro|||0000-0001-9888-8754
Cladera i Cerdà, Josep|||0000-0002-1724-3477
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Biochemistry
Biophysics
Structural biology
topic Biochemistry
Biophysics
Structural biology
description Amyloid plaques composed of Aβ amyloid peptides and neurofibrillary tangles are a pathological hallmark of Alzheimer's disease. In situ identification of early-stage amyloid aggregates in Alzheimer's disease is relevant for their importance as potential targets for effective drugs. Synchrotron-based infrared imaging is here used to identify early-stage oligomeric/granular aggregated amyloid species in situ in the brain of APP/PS1 transgenic mice and Octodon degus for the first time. Also, APP/PS1 mice show fibrillary aggregates at 6 and 12 months whereas very little formation of fibrils is found in aged Octodon degus. Finally, significant decreased burden of early-stage aggregates and fibrillary aggregates is obtained following treatment with G4-His-Mal dendrimers (a neurodegenerative protector) in 6-month-old APP/PS1 mice, thus demonstrating putative therapeutic properties of G4-His-Mal dendrimers in AD models. Identification, localization, and characterization using infrared imaging of these non-fibrillary species in the cerebral cortex at early stages of AD progression in transgenic mice point to their relevance as putative pharmacological targets. No less important, early detection of these structures may be useful in the search for markers for non-invasive diagnostic techniques.
publishDate 2020
dc.date.none.fl_str_mv 2
2020-01-01
2020
2020-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/252533
https://dx.doi.org/urn:doi:10.1038/s41598-020-62708-2
url https://ddd.uab.cat/record/252533
https://dx.doi.org/urn:doi:10.1038/s41598-020-62708-2
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Ministerio de Ciencia, Innovación y Universidades https://doi.org/10.13039/100014440 SAF2017-844-R
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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