Amyloid-β peptide remnants in AN-1792-immunized Alzheimer's disease patients: A biochemical analysis

Autores: Patton, R. Lyle; Kalback, Walter M.; Esh, Chera L.; Kokjohn, Tyler A.; Van Vickle, Gregory D.; Luehrs, Dean C.; Kuo, Yu-Min; Lopez, John; Brune, Daniel; Ferrer, Isidro; Masliah, Eliezer; Newel, Amanda J.; Beach, Thomas G.; Castaño, Eduardo Miguel; Roher, Alex E.
Año de publicación: 2006
Idioma: inglés
Tipo de recurso: artículo
Estado: versión publicada
Descripción: Experiments with amyloid-β (Aβ)-42-immunized transgenic mouse models of Alzheimer's disease have revealed amyloid plaque disruption and apparent cognitive function recovery. Neuropathological examination of patients vaccinated against purified Aβ-42 (AN-1792) has demonstrated that senile plaque disruption occurred in immunized humans as well. Here, we examined tissue histology and quantified and biochemically characterized the remnant amyloid peptides in the gray and white matter and leptomeningeal/cortical vessels of two AN-1792-vaccinated patients, one of whom developed meningoencephalitis. Compact core and diffuse amyloid deposits in both vaccinated individuals were focally absent in some regions. Although parenchymal amyloid was focally disaggregated, vascular deposits were relatively preserved or even increased. Immunoassay revealed that total soluble amyloid levels were sharply elevated in vaccinated patient gray and white matter compared with Alzheimer's disease cases. Our experiments suggest that although immunization disrupted amyloid deposits, vascular capture prevented large-scale egress of Aβ peptides. Trapped, solubilized amyloid peptides may ultimately have cascading toxic effects on cerebrovascular, gray and white matter tissues. Anti-amyloid immunization may be most effective not as therapeutic or mitigating measures but as a prophylactic measure when Aβ deposition is still minimal. This may allow Aβ mobilization under conditions in which drainage and degradation of these toxic peptides is efficient.
Fil: Patton, R. Lyle. Banner Sun Health Research Institute; Estados Unidos
Fil: Kalback, Walter M.. Banner Sun Health Research Institute; Estados Unidos
Fil: Esh, Chera L.. Banner Sun Health Research Institute; Estados Unidos
Fil: Kokjohn, Tyler A.. Midwestern University Glendale; Estados Unidos. Banner Sun Health Research Institute; Estados Unidos
Fil: Van Vickle, Gregory D.. Banner Sun Health Research Institute; Estados Unidos
Fil: Luehrs, Dean C.. National Cheng Kung University; China
Fil: Kuo, Yu-Min. Banner Sun Health Research Institute; Estados Unidos
Fil: Lopez, John. Arizona State University; Estados Unidos
Fil: Brune, Daniel. Arizona State University; Estados Unidos
Fil: Ferrer, Isidro. Hospital Universitari de Bellvitge; España
Fil: Masliah, Eliezer. University of California at San Diego; Estados Unidos
Fil: Newel, Amanda J.. Banner Sun Health Research Institute; Estados Unidos
Fil: Beach, Thomas G.. Banner Sun Health Research Institute; 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.. Banner Sun Health Research Institute; Estados Unidos
Materia: Alzheimer
Vaccination
Amyloid Beta
Nivel de accesibilidad: acceso abierto
Condiciones de uso: https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
Institución: Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador: oai:ri.conicet.gov.ar:11336/39733

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spelling	Amyloid-β peptide remnants in AN-1792-immunized Alzheimer's disease patients: A biochemical analysisPatton, R. LyleKalback, Walter M.Esh, Chera L.Kokjohn, Tyler A.Van Vickle, Gregory D.Luehrs, Dean C.Kuo, Yu-MinLopez, JohnBrune, DanielFerrer, IsidroMasliah, EliezerNewel, Amanda J.Beach, Thomas G.Castaño, Eduardo MiguelRoher, Alex E.AlzheimerVaccinationAmyloid Betahttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Experiments with amyloid-β (Aβ)-42-immunized transgenic mouse models of Alzheimer's disease have revealed amyloid plaque disruption and apparent cognitive function recovery. Neuropathological examination of patients vaccinated against purified Aβ-42 (AN-1792) has demonstrated that senile plaque disruption occurred in immunized humans as well. Here, we examined tissue histology and quantified and biochemically characterized the remnant amyloid peptides in the gray and white matter and leptomeningeal/cortical vessels of two AN-1792-vaccinated patients, one of whom developed meningoencephalitis. Compact core and diffuse amyloid deposits in both vaccinated individuals were focally absent in some regions. Although parenchymal amyloid was focally disaggregated, vascular deposits were relatively preserved or even increased. Immunoassay revealed that total soluble amyloid levels were sharply elevated in vaccinated patient gray and white matter compared with Alzheimer's disease cases. Our experiments suggest that although immunization disrupted amyloid deposits, vascular capture prevented large-scale egress of Aβ peptides. Trapped, solubilized amyloid peptides may ultimately have cascading toxic effects on cerebrovascular, gray and white matter tissues. Anti-amyloid immunization may be most effective not as therapeutic or mitigating measures but as a prophylactic measure when Aβ deposition is still minimal. This may allow Aβ mobilization under conditions in which drainage and degradation of these toxic peptides is efficient.Fil: Patton, R. Lyle. Banner Sun Health Research Institute; Estados UnidosFil: Kalback, Walter M.. Banner Sun Health Research Institute; Estados UnidosFil: Esh, Chera L.. Banner Sun Health Research Institute; Estados UnidosFil: Kokjohn, Tyler A.. Midwestern University Glendale; Estados Unidos. Banner Sun Health Research Institute; Estados UnidosFil: Van Vickle, Gregory D.. Banner Sun Health Research Institute; Estados UnidosFil: Luehrs, Dean C.. National Cheng Kung University; ChinaFil: Kuo, Yu-Min. Banner Sun Health Research Institute; Estados UnidosFil: Lopez, John. Arizona State University; Estados UnidosFil: Brune, Daniel. Arizona State University; Estados UnidosFil: Ferrer, Isidro. Hospital Universitari de Bellvitge; EspañaFil: Masliah, Eliezer. University of California at San Diego; Estados UnidosFil: Newel, Amanda J.. Banner Sun Health Research Institute; Estados UnidosFil: Beach, Thomas G.. Banner Sun Health Research Institute; 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.. Banner Sun Health Research Institute; Estados UnidosAmer Soc Investigative Pathology, Inc2006-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/39733Patton, R. Lyle; Kalback, Walter M.; Esh, Chera L.; Kokjohn, Tyler A.; Van Vickle, Gregory D.; et al.; Amyloid-β peptide remnants in AN-1792-immunized Alzheimer's disease patients: A biochemical analysis; Amer Soc Investigative Pathology, Inc; American Journal Of Pathology; 169; 3; 12-2006; 1048-10630002-94401525-2191CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S0002-9440(10)62779-4info:eu-repo/semantics/altIdentifier/doi/10.2353/ajpath.2006.060269info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:58:29Zoai:ri.conicet.gov.ar:11336/39733instacron: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:34982025-09-03 09:58:30.176CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv	Amyloid-β peptide remnants in AN-1792-immunized Alzheimer's disease patients: A biochemical analysis
title	Amyloid-β peptide remnants in AN-1792-immunized Alzheimer's disease patients: A biochemical analysis
spellingShingle	Amyloid-β peptide remnants in AN-1792-immunized Alzheimer's disease patients: A biochemical analysis Patton, R. Lyle Alzheimer Vaccination Amyloid Beta
title_short	Amyloid-β peptide remnants in AN-1792-immunized Alzheimer's disease patients: A biochemical analysis
title_full	Amyloid-β peptide remnants in AN-1792-immunized Alzheimer's disease patients: A biochemical analysis
title_fullStr	Amyloid-β peptide remnants in AN-1792-immunized Alzheimer's disease patients: A biochemical analysis
title_full_unstemmed	Amyloid-β peptide remnants in AN-1792-immunized Alzheimer's disease patients: A biochemical analysis
title_sort	Amyloid-β peptide remnants in AN-1792-immunized Alzheimer's disease patients: A biochemical analysis
dc.creator.none.fl_str_mv	Patton, R. Lyle Kalback, Walter M. Esh, Chera L. Kokjohn, Tyler A. Van Vickle, Gregory D. Luehrs, Dean C. Kuo, Yu-Min Lopez, John Brune, Daniel Ferrer, Isidro Masliah, Eliezer Newel, Amanda J. Beach, Thomas G. Castaño, Eduardo Miguel Roher, Alex E.
author	Patton, R. Lyle
author_facet	Patton, R. Lyle Kalback, Walter M. Esh, Chera L. Kokjohn, Tyler A. Van Vickle, Gregory D. Luehrs, Dean C. Kuo, Yu-Min Lopez, John Brune, Daniel Ferrer, Isidro Masliah, Eliezer Newel, Amanda J. Beach, Thomas G. Castaño, Eduardo Miguel Roher, Alex E.
author_role	author
author2	Kalback, Walter M. Esh, Chera L. Kokjohn, Tyler A. Van Vickle, Gregory D. Luehrs, Dean C. Kuo, Yu-Min Lopez, John Brune, Daniel Ferrer, Isidro Masliah, Eliezer Newel, Amanda J. Beach, Thomas G. Castaño, Eduardo Miguel Roher, Alex E.
author2_role	author author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	Alzheimer Vaccination Amyloid Beta
topic	Alzheimer Vaccination Amyloid Beta
purl_subject.fl_str_mv	https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv	Experiments with amyloid-β (Aβ)-42-immunized transgenic mouse models of Alzheimer's disease have revealed amyloid plaque disruption and apparent cognitive function recovery. Neuropathological examination of patients vaccinated against purified Aβ-42 (AN-1792) has demonstrated that senile plaque disruption occurred in immunized humans as well. Here, we examined tissue histology and quantified and biochemically characterized the remnant amyloid peptides in the gray and white matter and leptomeningeal/cortical vessels of two AN-1792-vaccinated patients, one of whom developed meningoencephalitis. Compact core and diffuse amyloid deposits in both vaccinated individuals were focally absent in some regions. Although parenchymal amyloid was focally disaggregated, vascular deposits were relatively preserved or even increased. Immunoassay revealed that total soluble amyloid levels were sharply elevated in vaccinated patient gray and white matter compared with Alzheimer's disease cases. Our experiments suggest that although immunization disrupted amyloid deposits, vascular capture prevented large-scale egress of Aβ peptides. Trapped, solubilized amyloid peptides may ultimately have cascading toxic effects on cerebrovascular, gray and white matter tissues. Anti-amyloid immunization may be most effective not as therapeutic or mitigating measures but as a prophylactic measure when Aβ deposition is still minimal. This may allow Aβ mobilization under conditions in which drainage and degradation of these toxic peptides is efficient. Fil: Patton, R. Lyle. Banner Sun Health Research Institute; Estados Unidos Fil: Kalback, Walter M.. Banner Sun Health Research Institute; Estados Unidos Fil: Esh, Chera L.. Banner Sun Health Research Institute; Estados Unidos Fil: Kokjohn, Tyler A.. Midwestern University Glendale; Estados Unidos. Banner Sun Health Research Institute; Estados Unidos Fil: Van Vickle, Gregory D.. Banner Sun Health Research Institute; Estados Unidos Fil: Luehrs, Dean C.. National Cheng Kung University; China Fil: Kuo, Yu-Min. Banner Sun Health Research Institute; Estados Unidos Fil: Lopez, John. Arizona State University; Estados Unidos Fil: Brune, Daniel. Arizona State University; Estados Unidos Fil: Ferrer, Isidro. Hospital Universitari de Bellvitge; España Fil: Masliah, Eliezer. University of California at San Diego; Estados Unidos Fil: Newel, Amanda J.. Banner Sun Health Research Institute; Estados Unidos Fil: Beach, Thomas G.. Banner Sun Health Research Institute; 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.. Banner Sun Health Research Institute; Estados Unidos
description	Experiments with amyloid-β (Aβ)-42-immunized transgenic mouse models of Alzheimer's disease have revealed amyloid plaque disruption and apparent cognitive function recovery. Neuropathological examination of patients vaccinated against purified Aβ-42 (AN-1792) has demonstrated that senile plaque disruption occurred in immunized humans as well. Here, we examined tissue histology and quantified and biochemically characterized the remnant amyloid peptides in the gray and white matter and leptomeningeal/cortical vessels of two AN-1792-vaccinated patients, one of whom developed meningoencephalitis. Compact core and diffuse amyloid deposits in both vaccinated individuals were focally absent in some regions. Although parenchymal amyloid was focally disaggregated, vascular deposits were relatively preserved or even increased. Immunoassay revealed that total soluble amyloid levels were sharply elevated in vaccinated patient gray and white matter compared with Alzheimer's disease cases. Our experiments suggest that although immunization disrupted amyloid deposits, vascular capture prevented large-scale egress of Aβ peptides. Trapped, solubilized amyloid peptides may ultimately have cascading toxic effects on cerebrovascular, gray and white matter tissues. Anti-amyloid immunization may be most effective not as therapeutic or mitigating measures but as a prophylactic measure when Aβ deposition is still minimal. This may allow Aβ mobilization under conditions in which drainage and degradation of these toxic peptides is efficient.
publishDate	2006
dc.date.none.fl_str_mv	2006-12
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/11336/39733 Patton, R. Lyle; Kalback, Walter M.; Esh, Chera L.; Kokjohn, Tyler A.; Van Vickle, Gregory D.; et al.; Amyloid-β peptide remnants in AN-1792-immunized Alzheimer's disease patients: A biochemical analysis; Amer Soc Investigative Pathology, Inc; American Journal Of Pathology; 169; 3; 12-2006; 1048-1063 0002-9440 1525-2191 CONICET Digital CONICET
url	http://hdl.handle.net/11336/39733
identifier_str_mv	Patton, R. Lyle; Kalback, Walter M.; Esh, Chera L.; Kokjohn, Tyler A.; Van Vickle, Gregory D.; et al.; Amyloid-β peptide remnants in AN-1792-immunized Alzheimer's disease patients: A biochemical analysis; Amer Soc Investigative Pathology, Inc; American Journal Of Pathology; 169; 3; 12-2006; 1048-1063 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/https://linkinghub.elsevier.com/retrieve/pii/S0002-9440(10)62779-4 info:eu-repo/semantics/altIdentifier/doi/10.2353/ajpath.2006.060269
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)
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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
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Amyloid-β peptide remnants in AN-1792-immunized Alzheimer's disease patients: A biochemical analysis

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