Atherosclerosis, vascular amyloidosis and brain hypoperfusion in the pathogenesis of sporadic Alzheimer's disease

Autores
Kalback, Walter; Esh, Chera; Castaño, Eduardo Miguel; Rahman, Afroza; Kokjohn, Tyler; Luehrs, Dean C.; Sue, Lucia; Cisneros, Raquel; Gerber, Francoise; Richardson, Claudia; Bohrmann, Bernd; Walker, Douglas G.; Beach, Thomas G.; Roher, Alex E.
Año de publicación
2004
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
We postulate that severe atherosclerotic occlusion of the circle of Willis and leptomeningeal arteries is an important factor in the pathogenesis of some sporadic Alzheimer's disease (AD) cases. These arterial stenoses are complicated by an overwhelming amyloid accumulation in the walls of leptomeningeal and cortical arteries resulting in a significant decrease in perfusion pressure and consequent ischemia/hypoxia of the brain tissue. We also propose that the distal areas of the white matter (WM) will be the first affected by a lack of oxygen and nutrients. Our hypotheses are supported by the following observations: (1) the number of stenoses is more frequent in AD than in the control population (p = 0.008); (2) the average index of occlusion is greater in AD than in the control group (p < 0.00001); (3) the index of stenosis and the total number of stenoses per case are positively correlated (R = 0.67); (4) the index of stenosis correlates with the neuropathological lesions of AD and with the MMSE psychometric test; (5) the number and degree of atherosclerosis of the anterior, middle and posterior cerebral arteries is more severe in cases of AD than in the control population; (6) atherosclerosis severity is apparently associated with the severity of the vascular amyloidosis; (7) the WM rarefaction correlates with the severity of the atherosclerosis and vascular amyloidosis; (8) the total cell count and microvessel count in the areas of WM rarefaction correlate with the neuropathological lesions of AD and with the MMSE score. Our data strongly suggest that severe hemodynamic disturbances contribute to sporadic AD and support the numerous observations indicating cardiovascular system participation in the pathogenesis of these dementias.
Fil: Kalback, Walter. Sun Health Research Institute; Estados Unidos
Fil: Esh, Chera. Sun Health Research Institute; Estados Unidos
Fil: Castaño, Eduardo Miguel. Sun Health Research Institute; Estados Unidos. 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. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Rahman, Afroza. Sun Health Research Institute; Estados Unidos
Fil: Kokjohn, Tyler. Midwestern University; Estados Unidos
Fil: Luehrs, Dean C.. Sun Health Research Institute; Estados Unidos
Fil: Sue, Lucia. Sun Health Research Institute; Estados Unidos
Fil: Cisneros, Raquel. Sun Health Research Institute; Estados Unidos
Fil: Gerber, Francoise. La Roche Ltd.; Suiza
Fil: Richardson, Claudia. La Roche Ltd.; Suiza
Fil: Bohrmann, Bernd. La Roche Ltd.; Suiza
Fil: Walker, Douglas G.. Sun Health Research Institute; Estados Unidos
Fil: Beach, Thomas G.. Sun Health Research Institute; Estados Unidos
Fil: Roher, Alex E.. Sun Health Research Institute; Estados Unidos
Materia
Alzheimer'S Disease
Atherosclerosis
Vascular Amyloidosis
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:11336/43568
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/43568
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Atherosclerosis, vascular amyloidosis and brain hypoperfusion in the pathogenesis of sporadic Alzheimer's diseaseKalback, WalterEsh, CheraCastaño, Eduardo MiguelRahman, AfrozaKokjohn, TylerLuehrs, Dean C.Sue, LuciaCisneros, RaquelGerber, FrancoiseRichardson, ClaudiaBohrmann, BerndWalker, Douglas G.Beach, Thomas G.Roher, Alex E.Alzheimer'S DiseaseAtherosclerosisVascular Amyloidosishttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1We postulate that severe atherosclerotic occlusion of the circle of Willis and leptomeningeal arteries is an important factor in the pathogenesis of some sporadic Alzheimer's disease (AD) cases. These arterial stenoses are complicated by an overwhelming amyloid accumulation in the walls of leptomeningeal and cortical arteries resulting in a significant decrease in perfusion pressure and consequent ischemia/hypoxia of the brain tissue. We also propose that the distal areas of the white matter (WM) will be the first affected by a lack of oxygen and nutrients. Our hypotheses are supported by the following observations: (1) the number of stenoses is more frequent in AD than in the control population (p = 0.008); (2) the average index of occlusion is greater in AD than in the control group (p < 0.00001); (3) the index of stenosis and the total number of stenoses per case are positively correlated (R = 0.67); (4) the index of stenosis correlates with the neuropathological lesions of AD and with the MMSE psychometric test; (5) the number and degree of atherosclerosis of the anterior, middle and posterior cerebral arteries is more severe in cases of AD than in the control population; (6) atherosclerosis severity is apparently associated with the severity of the vascular amyloidosis; (7) the WM rarefaction correlates with the severity of the atherosclerosis and vascular amyloidosis; (8) the total cell count and microvessel count in the areas of WM rarefaction correlate with the neuropathological lesions of AD and with the MMSE score. Our data strongly suggest that severe hemodynamic disturbances contribute to sporadic AD and support the numerous observations indicating cardiovascular system participation in the pathogenesis of these dementias.Fil: Kalback, Walter. Sun Health Research Institute; Estados UnidosFil: Esh, Chera. Sun Health Research Institute; Estados UnidosFil: Castaño, Eduardo Miguel. Sun Health Research Institute; Estados Unidos. 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. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Rahman, Afroza. Sun Health Research Institute; Estados UnidosFil: Kokjohn, Tyler. Midwestern University; Estados UnidosFil: Luehrs, Dean C.. Sun Health Research Institute; Estados UnidosFil: Sue, Lucia. Sun Health Research Institute; Estados UnidosFil: Cisneros, Raquel. Sun Health Research Institute; Estados UnidosFil: Gerber, Francoise. La Roche Ltd.; SuizaFil: Richardson, Claudia. La Roche Ltd.; SuizaFil: Bohrmann, Bernd. La Roche Ltd.; SuizaFil: Walker, Douglas G.. Sun Health Research Institute; Estados UnidosFil: Beach, Thomas G.. Sun Health Research Institute; Estados UnidosFil: Roher, Alex E.. Sun Health Research Institute; Estados UnidosManey Publishing2004-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/43568Kalback, Walter; Esh, Chera; Castaño, Eduardo Miguel; Rahman, Afroza; Kokjohn, Tyler; et al.; Atherosclerosis, vascular amyloidosis and brain hypoperfusion in the pathogenesis of sporadic Alzheimer's disease; Maney Publishing; Neurological Research; 26; 5; 7-2004; 525-5390161-64121743-1328CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.tandfonline.com/doi/abs/10.1179/016164104225017668info:eu-repo/semantics/altIdentifier/doi/10.1179/016164104225017668info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:46:05Zoai:ri.conicet.gov.ar:11336/43568instacron: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 09:46:05.847CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Atherosclerosis, vascular amyloidosis and brain hypoperfusion in the pathogenesis of sporadic Alzheimer's disease
title Atherosclerosis, vascular amyloidosis and brain hypoperfusion in the pathogenesis of sporadic Alzheimer's disease
spellingShingle Atherosclerosis, vascular amyloidosis and brain hypoperfusion in the pathogenesis of sporadic Alzheimer's disease
Kalback, Walter
Alzheimer'S Disease
Atherosclerosis
Vascular Amyloidosis
title_short Atherosclerosis, vascular amyloidosis and brain hypoperfusion in the pathogenesis of sporadic Alzheimer's disease
title_full Atherosclerosis, vascular amyloidosis and brain hypoperfusion in the pathogenesis of sporadic Alzheimer's disease
title_fullStr Atherosclerosis, vascular amyloidosis and brain hypoperfusion in the pathogenesis of sporadic Alzheimer's disease
title_full_unstemmed Atherosclerosis, vascular amyloidosis and brain hypoperfusion in the pathogenesis of sporadic Alzheimer's disease
title_sort Atherosclerosis, vascular amyloidosis and brain hypoperfusion in the pathogenesis of sporadic Alzheimer's disease
dc.creator.none.fl_str_mv Kalback, Walter
Esh, Chera
Castaño, Eduardo Miguel
Rahman, Afroza
Kokjohn, Tyler
Luehrs, Dean C.
Sue, Lucia
Cisneros, Raquel
Gerber, Francoise
Richardson, Claudia
Bohrmann, Bernd
Walker, Douglas G.
Beach, Thomas G.
Roher, Alex E.
author Kalback, Walter
author_facet Kalback, Walter
Esh, Chera
Castaño, Eduardo Miguel
Rahman, Afroza
Kokjohn, Tyler
Luehrs, Dean C.
Sue, Lucia
Cisneros, Raquel
Gerber, Francoise
Richardson, Claudia
Bohrmann, Bernd
Walker, Douglas G.
Beach, Thomas G.
Roher, Alex E.
author_role author
author2 Esh, Chera
Castaño, Eduardo Miguel
Rahman, Afroza
Kokjohn, Tyler
Luehrs, Dean C.
Sue, Lucia
Cisneros, Raquel
Gerber, Francoise
Richardson, Claudia
Bohrmann, Bernd
Walker, Douglas G.
Beach, Thomas G.
Roher, Alex E.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Alzheimer'S Disease
Atherosclerosis
Vascular Amyloidosis
topic Alzheimer'S Disease
Atherosclerosis
Vascular Amyloidosis
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv We postulate that severe atherosclerotic occlusion of the circle of Willis and leptomeningeal arteries is an important factor in the pathogenesis of some sporadic Alzheimer's disease (AD) cases. These arterial stenoses are complicated by an overwhelming amyloid accumulation in the walls of leptomeningeal and cortical arteries resulting in a significant decrease in perfusion pressure and consequent ischemia/hypoxia of the brain tissue. We also propose that the distal areas of the white matter (WM) will be the first affected by a lack of oxygen and nutrients. Our hypotheses are supported by the following observations: (1) the number of stenoses is more frequent in AD than in the control population (p = 0.008); (2) the average index of occlusion is greater in AD than in the control group (p < 0.00001); (3) the index of stenosis and the total number of stenoses per case are positively correlated (R = 0.67); (4) the index of stenosis correlates with the neuropathological lesions of AD and with the MMSE psychometric test; (5) the number and degree of atherosclerosis of the anterior, middle and posterior cerebral arteries is more severe in cases of AD than in the control population; (6) atherosclerosis severity is apparently associated with the severity of the vascular amyloidosis; (7) the WM rarefaction correlates with the severity of the atherosclerosis and vascular amyloidosis; (8) the total cell count and microvessel count in the areas of WM rarefaction correlate with the neuropathological lesions of AD and with the MMSE score. Our data strongly suggest that severe hemodynamic disturbances contribute to sporadic AD and support the numerous observations indicating cardiovascular system participation in the pathogenesis of these dementias.
Fil: Kalback, Walter. Sun Health Research Institute; Estados Unidos
Fil: Esh, Chera. Sun Health Research Institute; Estados Unidos
Fil: Castaño, Eduardo Miguel. Sun Health Research Institute; Estados Unidos. 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. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Rahman, Afroza. Sun Health Research Institute; Estados Unidos
Fil: Kokjohn, Tyler. Midwestern University; Estados Unidos
Fil: Luehrs, Dean C.. Sun Health Research Institute; Estados Unidos
Fil: Sue, Lucia. Sun Health Research Institute; Estados Unidos
Fil: Cisneros, Raquel. Sun Health Research Institute; Estados Unidos
Fil: Gerber, Francoise. La Roche Ltd.; Suiza
Fil: Richardson, Claudia. La Roche Ltd.; Suiza
Fil: Bohrmann, Bernd. La Roche Ltd.; Suiza
Fil: Walker, Douglas G.. Sun Health Research Institute; Estados Unidos
Fil: Beach, Thomas G.. Sun Health Research Institute; Estados Unidos
Fil: Roher, Alex E.. Sun Health Research Institute; Estados Unidos
description We postulate that severe atherosclerotic occlusion of the circle of Willis and leptomeningeal arteries is an important factor in the pathogenesis of some sporadic Alzheimer's disease (AD) cases. These arterial stenoses are complicated by an overwhelming amyloid accumulation in the walls of leptomeningeal and cortical arteries resulting in a significant decrease in perfusion pressure and consequent ischemia/hypoxia of the brain tissue. We also propose that the distal areas of the white matter (WM) will be the first affected by a lack of oxygen and nutrients. Our hypotheses are supported by the following observations: (1) the number of stenoses is more frequent in AD than in the control population (p = 0.008); (2) the average index of occlusion is greater in AD than in the control group (p < 0.00001); (3) the index of stenosis and the total number of stenoses per case are positively correlated (R = 0.67); (4) the index of stenosis correlates with the neuropathological lesions of AD and with the MMSE psychometric test; (5) the number and degree of atherosclerosis of the anterior, middle and posterior cerebral arteries is more severe in cases of AD than in the control population; (6) atherosclerosis severity is apparently associated with the severity of the vascular amyloidosis; (7) the WM rarefaction correlates with the severity of the atherosclerosis and vascular amyloidosis; (8) the total cell count and microvessel count in the areas of WM rarefaction correlate with the neuropathological lesions of AD and with the MMSE score. Our data strongly suggest that severe hemodynamic disturbances contribute to sporadic AD and support the numerous observations indicating cardiovascular system participation in the pathogenesis of these dementias.
publishDate 2004
dc.date.none.fl_str_mv 2004-07
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/11336/43568
Kalback, Walter; Esh, Chera; Castaño, Eduardo Miguel; Rahman, Afroza; Kokjohn, Tyler; et al.; Atherosclerosis, vascular amyloidosis and brain hypoperfusion in the pathogenesis of sporadic Alzheimer's disease; Maney Publishing; Neurological Research; 26; 5; 7-2004; 525-539
0161-6412
1743-1328
CONICET Digital
CONICET
url http://hdl.handle.net/11336/43568
identifier_str_mv Kalback, Walter; Esh, Chera; Castaño, Eduardo Miguel; Rahman, Afroza; Kokjohn, Tyler; et al.; Atherosclerosis, vascular amyloidosis and brain hypoperfusion in the pathogenesis of sporadic Alzheimer's disease; Maney Publishing; Neurological Research; 26; 5; 7-2004; 525-539
0161-6412
1743-1328
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://www.tandfonline.com/doi/abs/10.1179/016164104225017668
info:eu-repo/semantics/altIdentifier/doi/10.1179/016164104225017668
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 Maney Publishing
publisher.none.fl_str_mv Maney Publishing
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_ 1842268773505040384
score 13.13397

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