Tg-SwDI transgenic mice exhibit novel alterations in AbetaPP processing, Abeta degradation, and resilient amyloid angiopathy

Autores
Van Vickle, Gregory D.; Esh, Chera L.; Daugs, Ian D.; Kokjohn, Tyler A.; Kalback, Walter M.; Patton, R. Lyle; Luehrs, Dean C.; Walker, Douglas G.; Lue, Lih-Fen; Beach, Thomas G.; Davis, Judianne; Van Nostrand, William E.; Castaño, Eduardo Miguel; Roher, Alex E.
Año de publicación
2008
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Alzheimer's disease (AD) is characterized by the accumulation of extracellular insoluble amyloid, primarily derived from polymerized amyloid-beta (Abeta) peptides. We characterized the chemical composition of the Abeta peptides deposited in the brain parenchyma and cerebrovascular walls of triple transgenic Tg-SwDI mice that produce a rapid and profuse Abeta accumulation. The processing of the N- and C-terminal regions of mutant AbetaPP differs substantially from humans because the brain parenchyma accumulates numerous, diffuse, nonfibrillar plaques, whereas the thalamic microvessels harbor overwhelming amounts of compact, fibrillar, thioflavine-S- and apolipoprotein E-positive amyloid deposits. The abundant accretion of vascular amyloid, despite low AbetaPP transgene expression levels, suggests that inefficient Abeta proteolysis because of conformational changes and dimerization may be key pathogenic factors in this animal model. The disruption of amyloid plaque cores by immunotherapy is accompanied by increased perivascular deposition in both humans and transgenic mice. This analogous susceptibility and response to the disruption of amyloid deposits suggests that Tg-SwDI mice provide an excellent model in which to study the functional aftermath of immunotherapeutic interventions. These mice might also reveal new avenues to promote amyloidogenic AbetaPP processing and fundamental insights into the faulty degradation and clearance of Abeta in AD, pivotal issues in understanding AD pathophysiology and the assessment of new therapeutic agents.
Fil: Van Vickle, Gregory D.. Sun Health Research Institute; Estados Unidos
Fil: Esh, Chera L.. Sun Health Research Institute; Estados Unidos
Fil: Daugs, Ian D.. Sun Health Research Institute; Estados Unidos
Fil: Kokjohn, Tyler A.. Midwestern University; Estados Unidos
Fil: Kalback, Walter M.. Sun Health Research Institute; Estados Unidos
Fil: Patton, R. Lyle. Sun Health Research Institute; Estados Unidos
Fil: Luehrs, Dean C.. Sun Health Research Institute; Estados Unidos
Fil: Walker, Douglas G.. Sun Health Research Institute; Estados Unidos
Fil: Lue, Lih-Fen. Sun Health Research Institute; Estados Unidos
Fil: Beach, Thomas G.. Sun Health Research Institute; Estados Unidos
Fil: Davis, Judianne. Stony Brook University; Estados Unidos
Fil: Van Nostrand, William E.. Stony Brook University; Estados Unidos
Fil: Castaño, Eduardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Roher, Alex E.. The Longtine Center for Molecular Biology and Genetics; Estados Unidos
Materia
Cerebrovascular Amyloidosis
Transgenic Mice
Swedish-Dutch Mutation
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/22693
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/22693
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Tg-SwDI transgenic mice exhibit novel alterations in AbetaPP processing, Abeta degradation, and resilient amyloid angiopathyVan Vickle, Gregory D.Esh, Chera L.Daugs, Ian D.Kokjohn, Tyler A.Kalback, Walter M.Patton, R. LyleLuehrs, Dean C.Walker, Douglas G.Lue, Lih-FenBeach, Thomas G.Davis, JudianneVan Nostrand, William E.Castaño, Eduardo MiguelRoher, Alex E.Cerebrovascular AmyloidosisTransgenic MiceSwedish-Dutch Mutationhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Alzheimer's disease (AD) is characterized by the accumulation of extracellular insoluble amyloid, primarily derived from polymerized amyloid-beta (Abeta) peptides. We characterized the chemical composition of the Abeta peptides deposited in the brain parenchyma and cerebrovascular walls of triple transgenic Tg-SwDI mice that produce a rapid and profuse Abeta accumulation. The processing of the N- and C-terminal regions of mutant AbetaPP differs substantially from humans because the brain parenchyma accumulates numerous, diffuse, nonfibrillar plaques, whereas the thalamic microvessels harbor overwhelming amounts of compact, fibrillar, thioflavine-S- and apolipoprotein E-positive amyloid deposits. The abundant accretion of vascular amyloid, despite low AbetaPP transgene expression levels, suggests that inefficient Abeta proteolysis because of conformational changes and dimerization may be key pathogenic factors in this animal model. The disruption of amyloid plaque cores by immunotherapy is accompanied by increased perivascular deposition in both humans and transgenic mice. This analogous susceptibility and response to the disruption of amyloid deposits suggests that Tg-SwDI mice provide an excellent model in which to study the functional aftermath of immunotherapeutic interventions. These mice might also reveal new avenues to promote amyloidogenic AbetaPP processing and fundamental insights into the faulty degradation and clearance of Abeta in AD, pivotal issues in understanding AD pathophysiology and the assessment of new therapeutic agents.Fil: Van Vickle, Gregory D.. Sun Health Research Institute; Estados UnidosFil: Esh, Chera L.. Sun Health Research Institute; Estados UnidosFil: Daugs, Ian D.. Sun Health Research Institute; Estados UnidosFil: Kokjohn, Tyler A.. Midwestern University; Estados UnidosFil: Kalback, Walter M.. Sun Health Research Institute; Estados UnidosFil: Patton, R. Lyle. Sun Health Research Institute; Estados UnidosFil: Luehrs, Dean C.. Sun Health Research Institute; Estados UnidosFil: Walker, Douglas G.. Sun Health Research Institute; Estados UnidosFil: Lue, Lih-Fen. Sun Health Research Institute; Estados UnidosFil: Beach, Thomas G.. Sun Health Research Institute; Estados UnidosFil: Davis, Judianne. Stony Brook University; Estados UnidosFil: Van Nostrand, William E.. Stony Brook University; Estados UnidosFil: Castaño, Eduardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Roher, Alex E.. The Longtine Center for Molecular Biology and Genetics; Estados UnidosAmer Soc Investigative Pathology, Inc2008-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/22693Van Vickle, Gregory D.; Esh, Chera L.; Daugs, Ian D.; Kokjohn, Tyler A.; Kalback, Walter M.; et al.; Tg-SwDI transgenic mice exhibit novel alterations in AbetaPP processing, Abeta degradation, and resilient amyloid angiopathy; Amer Soc Investigative Pathology, Inc; American Journal Of Pathology; 173; 2; 8-2008; 483-4930002-94401525-2191CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0002944010616240info:eu-repo/semantics/altIdentifier/doi/10.2353/ajpath.2008.071191info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:41:45Zoai:ri.conicet.gov.ar:11336/22693instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 11:41:45.794CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Tg-SwDI transgenic mice exhibit novel alterations in AbetaPP processing, Abeta degradation, and resilient amyloid angiopathy
title Tg-SwDI transgenic mice exhibit novel alterations in AbetaPP processing, Abeta degradation, and resilient amyloid angiopathy
spellingShingle Tg-SwDI transgenic mice exhibit novel alterations in AbetaPP processing, Abeta degradation, and resilient amyloid angiopathy
Van Vickle, Gregory D.
Cerebrovascular Amyloidosis
Transgenic Mice
Swedish-Dutch Mutation
title_short Tg-SwDI transgenic mice exhibit novel alterations in AbetaPP processing, Abeta degradation, and resilient amyloid angiopathy
title_full Tg-SwDI transgenic mice exhibit novel alterations in AbetaPP processing, Abeta degradation, and resilient amyloid angiopathy
title_fullStr Tg-SwDI transgenic mice exhibit novel alterations in AbetaPP processing, Abeta degradation, and resilient amyloid angiopathy
title_full_unstemmed Tg-SwDI transgenic mice exhibit novel alterations in AbetaPP processing, Abeta degradation, and resilient amyloid angiopathy
title_sort Tg-SwDI transgenic mice exhibit novel alterations in AbetaPP processing, Abeta degradation, and resilient amyloid angiopathy
dc.creator.none.fl_str_mv Van Vickle, Gregory D.
Esh, Chera L.
Daugs, Ian D.
Kokjohn, Tyler A.
Kalback, Walter M.
Patton, R. Lyle
Luehrs, Dean C.
Walker, Douglas G.
Lue, Lih-Fen
Beach, Thomas G.
Davis, Judianne
Van Nostrand, William E.
Castaño, Eduardo Miguel
Roher, Alex E.
author Van Vickle, Gregory D.
author_facet Van Vickle, Gregory D.
Esh, Chera L.
Daugs, Ian D.
Kokjohn, Tyler A.
Kalback, Walter M.
Patton, R. Lyle
Luehrs, Dean C.
Walker, Douglas G.
Lue, Lih-Fen
Beach, Thomas G.
Davis, Judianne
Van Nostrand, William E.
Castaño, Eduardo Miguel
Roher, Alex E.
author_role author
author2 Esh, Chera L.
Daugs, Ian D.
Kokjohn, Tyler A.
Kalback, Walter M.
Patton, R. Lyle
Luehrs, Dean C.
Walker, Douglas G.
Lue, Lih-Fen
Beach, Thomas G.
Davis, Judianne
Van Nostrand, William E.
Castaño, Eduardo Miguel
Roher, Alex E.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cerebrovascular Amyloidosis
Transgenic Mice
Swedish-Dutch Mutation
topic Cerebrovascular Amyloidosis
Transgenic Mice
Swedish-Dutch Mutation
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Alzheimer's disease (AD) is characterized by the accumulation of extracellular insoluble amyloid, primarily derived from polymerized amyloid-beta (Abeta) peptides. We characterized the chemical composition of the Abeta peptides deposited in the brain parenchyma and cerebrovascular walls of triple transgenic Tg-SwDI mice that produce a rapid and profuse Abeta accumulation. The processing of the N- and C-terminal regions of mutant AbetaPP differs substantially from humans because the brain parenchyma accumulates numerous, diffuse, nonfibrillar plaques, whereas the thalamic microvessels harbor overwhelming amounts of compact, fibrillar, thioflavine-S- and apolipoprotein E-positive amyloid deposits. The abundant accretion of vascular amyloid, despite low AbetaPP transgene expression levels, suggests that inefficient Abeta proteolysis because of conformational changes and dimerization may be key pathogenic factors in this animal model. The disruption of amyloid plaque cores by immunotherapy is accompanied by increased perivascular deposition in both humans and transgenic mice. This analogous susceptibility and response to the disruption of amyloid deposits suggests that Tg-SwDI mice provide an excellent model in which to study the functional aftermath of immunotherapeutic interventions. These mice might also reveal new avenues to promote amyloidogenic AbetaPP processing and fundamental insights into the faulty degradation and clearance of Abeta in AD, pivotal issues in understanding AD pathophysiology and the assessment of new therapeutic agents.
Fil: Van Vickle, Gregory D.. Sun Health Research Institute; Estados Unidos
Fil: Esh, Chera L.. Sun Health Research Institute; Estados Unidos
Fil: Daugs, Ian D.. Sun Health Research Institute; Estados Unidos
Fil: Kokjohn, Tyler A.. Midwestern University; Estados Unidos
Fil: Kalback, Walter M.. Sun Health Research Institute; Estados Unidos
Fil: Patton, R. Lyle. Sun Health Research Institute; Estados Unidos
Fil: Luehrs, Dean C.. Sun Health Research Institute; Estados Unidos
Fil: Walker, Douglas G.. Sun Health Research Institute; Estados Unidos
Fil: Lue, Lih-Fen. Sun Health Research Institute; Estados Unidos
Fil: Beach, Thomas G.. Sun Health Research Institute; Estados Unidos
Fil: Davis, Judianne. Stony Brook University; Estados Unidos
Fil: Van Nostrand, William E.. Stony Brook University; Estados Unidos
Fil: Castaño, Eduardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Roher, Alex E.. The Longtine Center for Molecular Biology and Genetics; Estados Unidos
description Alzheimer's disease (AD) is characterized by the accumulation of extracellular insoluble amyloid, primarily derived from polymerized amyloid-beta (Abeta) peptides. We characterized the chemical composition of the Abeta peptides deposited in the brain parenchyma and cerebrovascular walls of triple transgenic Tg-SwDI mice that produce a rapid and profuse Abeta accumulation. The processing of the N- and C-terminal regions of mutant AbetaPP differs substantially from humans because the brain parenchyma accumulates numerous, diffuse, nonfibrillar plaques, whereas the thalamic microvessels harbor overwhelming amounts of compact, fibrillar, thioflavine-S- and apolipoprotein E-positive amyloid deposits. The abundant accretion of vascular amyloid, despite low AbetaPP transgene expression levels, suggests that inefficient Abeta proteolysis because of conformational changes and dimerization may be key pathogenic factors in this animal model. The disruption of amyloid plaque cores by immunotherapy is accompanied by increased perivascular deposition in both humans and transgenic mice. This analogous susceptibility and response to the disruption of amyloid deposits suggests that Tg-SwDI mice provide an excellent model in which to study the functional aftermath of immunotherapeutic interventions. These mice might also reveal new avenues to promote amyloidogenic AbetaPP processing and fundamental insights into the faulty degradation and clearance of Abeta in AD, pivotal issues in understanding AD pathophysiology and the assessment of new therapeutic agents.
publishDate 2008
dc.date.none.fl_str_mv 2008-08
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/22693
Van Vickle, Gregory D.; Esh, Chera L.; Daugs, Ian D.; Kokjohn, Tyler A.; Kalback, Walter M.; et al.; Tg-SwDI transgenic mice exhibit novel alterations in AbetaPP processing, Abeta degradation, and resilient amyloid angiopathy; Amer Soc Investigative Pathology, Inc; American Journal Of Pathology; 173; 2; 8-2008; 483-493
0002-9440
1525-2191
CONICET Digital
CONICET
url http://hdl.handle.net/11336/22693
identifier_str_mv Van Vickle, Gregory D.; Esh, Chera L.; Daugs, Ian D.; Kokjohn, Tyler A.; Kalback, Walter M.; et al.; Tg-SwDI transgenic mice exhibit novel alterations in AbetaPP processing, Abeta degradation, and resilient amyloid angiopathy; Amer Soc Investigative Pathology, Inc; American Journal Of Pathology; 173; 2; 8-2008; 483-493
0002-9440
1525-2191
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0002944010616240
info:eu-repo/semantics/altIdentifier/doi/10.2353/ajpath.2008.071191
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Amer Soc Investigative Pathology, Inc
publisher.none.fl_str_mv Amer Soc Investigative Pathology, Inc
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1846782099626917888
score 12.982451

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