Alzheimer's disease and non-demented high pathology control nonagenarians: comparing and contrasting the biochemistry of cognitively successful aging

Autores
Maarouf, Chera L.; Daugs, Ian D.; Kokjohn, Tyler A.; Walker, Douglas G.; Hunter, Jesse M.; Kruchowsky, Jane C.; Woltjer, Randy; Kaye, Jeffrey; Castaño, Eduardo Miguel; Sabbagh, Marwan N.; Beach, Thomas G.; Roher, Alex E.
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The amyloid cascade hypothesis provides an economical mechanistic explanation for Alzheimer's disease (AD) dementia and correlated neuropathology. However, some nonagenarian individuals (high pathology controls, HPC) remain cognitively intact while enduring high amyloid plaque loads for decades. If amyloid accumulation is the prime instigator of neurotoxicity and dementia, specific protective mechanisms must enable these HPC to evade cognitive decline. We evaluated the neuropathological and biochemical differences existing between non-demented (ND)-HPC and an age-matched cohort with AD dementia. The ND-HPC selected for our study were clinically assessed as ND and possessed high amyloid plaque burdens. ELISA and Western blot analyses were used to quantify a group of proteins related to APP/Aβ/tau metabolism and other neurotrophic and inflammation-related molecules that have been found to be altered in neurodegenerative disorders and are pivotal to brain homeostasis and mental health. The molecules assumed to be critical in AD dementia, such as soluble or insoluble Aβ40, Aβ42 and tau were quantified by ELISA. Interestingly, only Aβ42 demonstrated a significant increase in ND-HPC when compared to the AD group. The vascular amyloid load which was not used in the selection of cases, was on the average almost 2-fold greater in AD than the ND-HPC, suggesting that a higher degree of microvascular dysfunction and perfusion compromise was present in the demented cohort. Neurofibrillary tangles were less frequent in the frontal cortices of ND-HPC. Biochemical findings included elevated vascular endothelial growth factor, apolipoprotein E and the neuroprotective factor S100B in ND-HPC, while anti-angiogenic pigment epithelium derived factor levels were lower. The lack of clear Aβ-related pathological/biochemical demarcation between AD and ND-HPC suggests that in addition to amyloid plaques other factors, such as neurofibrillary tangle density and vascular integrity, must play important roles in cognitive failure.
Fil: Maarouf, Chera L.. Banner Sun Health Research Institute. The Longtine Center for Neurodegenerative Biochemistry; Estados Unidos
Fil: Daugs, Ian D.. Banner Sun Health Research Institute. The Longtine Center for Neurodegenerative Biochemistry; Estados Unidos
Fil: Kokjohn, Tyler A.. Banner Sun Health Research Institute. The Longtine Center for Neurodegenerative Biochemistry; Estados Unidos. Midwestern University; Estados Unidos
Fil: Walker, Douglas G.. Banner Sun Health Research Institute. Laboratory of Neuroinflammation; Estados Unidos
Fil: Hunter, Jesse M.. Banner Sun Health Research Institute. The Longtine Center for Neurodegenerative Biochemistry; Estados Unidos
Fil: Kruchowsky, Jane C.. Banner Sun Health Research Institute. Laboratory of Neuroinflammation; Estados Unidos
Fil: Woltjer, Randy. Oregon Health & Science University. Department of Pathology; Estados Unidos
Fil: Kaye, Jeffrey. Oregon Health and Science University. Layton Aging and Alzheimer’s Disease Center; Estados Unidos
Fil: Castaño, Eduardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; Argentina
Fil: Sabbagh, Marwan N.. Banner Sun Health Research Institute. Cleo Roberts Center for Clinical Research; Estados Unidos
Fil: Beach, Thomas G.. Banner Sun Health Research Institute. Civin Laboratory for Neuropathology; Estados Unidos
Fil: Roher, Alex E.. Banner Sun Health Research Institute. The Longtine Center for Neurodegenerative Biochemistry; Estados Unidos
Materia
Alzheimer's disease
Aging
neuropathology
nonagenarians
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:11336/13820

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network_name_str CONICET Digital (CONICET)
spelling Alzheimer's disease and non-demented high pathology control nonagenarians: comparing and contrasting the biochemistry of cognitively successful agingMaarouf, Chera L.Daugs, Ian D.Kokjohn, Tyler A.Walker, Douglas G.Hunter, Jesse M.Kruchowsky, Jane C.Woltjer, RandyKaye, JeffreyCastaño, Eduardo MiguelSabbagh, Marwan N.Beach, Thomas G.Roher, Alex E.Alzheimer's diseaseAgingneuropathologynonagenarianshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The amyloid cascade hypothesis provides an economical mechanistic explanation for Alzheimer's disease (AD) dementia and correlated neuropathology. However, some nonagenarian individuals (high pathology controls, HPC) remain cognitively intact while enduring high amyloid plaque loads for decades. If amyloid accumulation is the prime instigator of neurotoxicity and dementia, specific protective mechanisms must enable these HPC to evade cognitive decline. We evaluated the neuropathological and biochemical differences existing between non-demented (ND)-HPC and an age-matched cohort with AD dementia. The ND-HPC selected for our study were clinically assessed as ND and possessed high amyloid plaque burdens. ELISA and Western blot analyses were used to quantify a group of proteins related to APP/Aβ/tau metabolism and other neurotrophic and inflammation-related molecules that have been found to be altered in neurodegenerative disorders and are pivotal to brain homeostasis and mental health. The molecules assumed to be critical in AD dementia, such as soluble or insoluble Aβ40, Aβ42 and tau were quantified by ELISA. Interestingly, only Aβ42 demonstrated a significant increase in ND-HPC when compared to the AD group. The vascular amyloid load which was not used in the selection of cases, was on the average almost 2-fold greater in AD than the ND-HPC, suggesting that a higher degree of microvascular dysfunction and perfusion compromise was present in the demented cohort. Neurofibrillary tangles were less frequent in the frontal cortices of ND-HPC. Biochemical findings included elevated vascular endothelial growth factor, apolipoprotein E and the neuroprotective factor S100B in ND-HPC, while anti-angiogenic pigment epithelium derived factor levels were lower. The lack of clear Aβ-related pathological/biochemical demarcation between AD and ND-HPC suggests that in addition to amyloid plaques other factors, such as neurofibrillary tangle density and vascular integrity, must play important roles in cognitive failure.Fil: Maarouf, Chera L.. Banner Sun Health Research Institute. The Longtine Center for Neurodegenerative Biochemistry; Estados UnidosFil: Daugs, Ian D.. Banner Sun Health Research Institute. The Longtine Center for Neurodegenerative Biochemistry; Estados UnidosFil: Kokjohn, Tyler A.. Banner Sun Health Research Institute. The Longtine Center for Neurodegenerative Biochemistry; Estados Unidos. Midwestern University; Estados UnidosFil: Walker, Douglas G.. Banner Sun Health Research Institute. Laboratory of Neuroinflammation; Estados UnidosFil: Hunter, Jesse M.. Banner Sun Health Research Institute. The Longtine Center for Neurodegenerative Biochemistry; Estados UnidosFil: Kruchowsky, Jane C.. Banner Sun Health Research Institute. Laboratory of Neuroinflammation; Estados UnidosFil: Woltjer, Randy. Oregon Health & Science University. Department of Pathology; Estados UnidosFil: Kaye, Jeffrey. Oregon Health and Science University. Layton Aging and Alzheimer’s Disease Center; Estados UnidosFil: Castaño, Eduardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; ArgentinaFil: Sabbagh, Marwan N.. Banner Sun Health Research Institute. Cleo Roberts Center for Clinical Research; Estados UnidosFil: Beach, Thomas G.. Banner Sun Health Research Institute. Civin Laboratory for Neuropathology; Estados UnidosFil: Roher, Alex E.. Banner Sun Health Research Institute. The Longtine Center for Neurodegenerative Biochemistry; Estados UnidosPublic Library Of Science2011info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/13820Maarouf, Chera L.; Daugs, Ian D.; Kokjohn, Tyler A.; Walker, Douglas G.; Hunter, Jesse M.; et al.; Alzheimer's disease and non-demented high pathology control nonagenarians: comparing and contrasting the biochemistry of cognitively successful aging; Public Library Of Science; Plos One; 6; 11; -1-2011; 1-171932-6203enginfo:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0027291info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0027291info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:41:21Zoai:ri.conicet.gov.ar:11336/13820instacron: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:34982025-09-29 09:41:22.034CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Alzheimer's disease and non-demented high pathology control nonagenarians: comparing and contrasting the biochemistry of cognitively successful aging
title Alzheimer's disease and non-demented high pathology control nonagenarians: comparing and contrasting the biochemistry of cognitively successful aging
spellingShingle Alzheimer's disease and non-demented high pathology control nonagenarians: comparing and contrasting the biochemistry of cognitively successful aging
Maarouf, Chera L.
Alzheimer's disease
Aging
neuropathology
nonagenarians
title_short Alzheimer's disease and non-demented high pathology control nonagenarians: comparing and contrasting the biochemistry of cognitively successful aging
title_full Alzheimer's disease and non-demented high pathology control nonagenarians: comparing and contrasting the biochemistry of cognitively successful aging
title_fullStr Alzheimer's disease and non-demented high pathology control nonagenarians: comparing and contrasting the biochemistry of cognitively successful aging
title_full_unstemmed Alzheimer's disease and non-demented high pathology control nonagenarians: comparing and contrasting the biochemistry of cognitively successful aging
title_sort Alzheimer's disease and non-demented high pathology control nonagenarians: comparing and contrasting the biochemistry of cognitively successful aging
dc.creator.none.fl_str_mv Maarouf, Chera L.
Daugs, Ian D.
Kokjohn, Tyler A.
Walker, Douglas G.
Hunter, Jesse M.
Kruchowsky, Jane C.
Woltjer, Randy
Kaye, Jeffrey
Castaño, Eduardo Miguel
Sabbagh, Marwan N.
Beach, Thomas G.
Roher, Alex E.
author Maarouf, Chera L.
author_facet Maarouf, Chera L.
Daugs, Ian D.
Kokjohn, Tyler A.
Walker, Douglas G.
Hunter, Jesse M.
Kruchowsky, Jane C.
Woltjer, Randy
Kaye, Jeffrey
Castaño, Eduardo Miguel
Sabbagh, Marwan N.
Beach, Thomas G.
Roher, Alex E.
author_role author
author2 Daugs, Ian D.
Kokjohn, Tyler A.
Walker, Douglas G.
Hunter, Jesse M.
Kruchowsky, Jane C.
Woltjer, Randy
Kaye, Jeffrey
Castaño, Eduardo Miguel
Sabbagh, Marwan N.
Beach, Thomas G.
Roher, Alex E.
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Alzheimer's disease
Aging
neuropathology
nonagenarians
topic Alzheimer's disease
Aging
neuropathology
nonagenarians
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The amyloid cascade hypothesis provides an economical mechanistic explanation for Alzheimer's disease (AD) dementia and correlated neuropathology. However, some nonagenarian individuals (high pathology controls, HPC) remain cognitively intact while enduring high amyloid plaque loads for decades. If amyloid accumulation is the prime instigator of neurotoxicity and dementia, specific protective mechanisms must enable these HPC to evade cognitive decline. We evaluated the neuropathological and biochemical differences existing between non-demented (ND)-HPC and an age-matched cohort with AD dementia. The ND-HPC selected for our study were clinically assessed as ND and possessed high amyloid plaque burdens. ELISA and Western blot analyses were used to quantify a group of proteins related to APP/Aβ/tau metabolism and other neurotrophic and inflammation-related molecules that have been found to be altered in neurodegenerative disorders and are pivotal to brain homeostasis and mental health. The molecules assumed to be critical in AD dementia, such as soluble or insoluble Aβ40, Aβ42 and tau were quantified by ELISA. Interestingly, only Aβ42 demonstrated a significant increase in ND-HPC when compared to the AD group. The vascular amyloid load which was not used in the selection of cases, was on the average almost 2-fold greater in AD than the ND-HPC, suggesting that a higher degree of microvascular dysfunction and perfusion compromise was present in the demented cohort. Neurofibrillary tangles were less frequent in the frontal cortices of ND-HPC. Biochemical findings included elevated vascular endothelial growth factor, apolipoprotein E and the neuroprotective factor S100B in ND-HPC, while anti-angiogenic pigment epithelium derived factor levels were lower. The lack of clear Aβ-related pathological/biochemical demarcation between AD and ND-HPC suggests that in addition to amyloid plaques other factors, such as neurofibrillary tangle density and vascular integrity, must play important roles in cognitive failure.
Fil: Maarouf, Chera L.. Banner Sun Health Research Institute. The Longtine Center for Neurodegenerative Biochemistry; Estados Unidos
Fil: Daugs, Ian D.. Banner Sun Health Research Institute. The Longtine Center for Neurodegenerative Biochemistry; Estados Unidos
Fil: Kokjohn, Tyler A.. Banner Sun Health Research Institute. The Longtine Center for Neurodegenerative Biochemistry; Estados Unidos. Midwestern University; Estados Unidos
Fil: Walker, Douglas G.. Banner Sun Health Research Institute. Laboratory of Neuroinflammation; Estados Unidos
Fil: Hunter, Jesse M.. Banner Sun Health Research Institute. The Longtine Center for Neurodegenerative Biochemistry; Estados Unidos
Fil: Kruchowsky, Jane C.. Banner Sun Health Research Institute. Laboratory of Neuroinflammation; Estados Unidos
Fil: Woltjer, Randy. Oregon Health & Science University. Department of Pathology; Estados Unidos
Fil: Kaye, Jeffrey. Oregon Health and Science University. Layton Aging and Alzheimer’s Disease Center; Estados Unidos
Fil: Castaño, Eduardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; Argentina
Fil: Sabbagh, Marwan N.. Banner Sun Health Research Institute. Cleo Roberts Center for Clinical Research; Estados Unidos
Fil: Beach, Thomas G.. Banner Sun Health Research Institute. Civin Laboratory for Neuropathology; Estados Unidos
Fil: Roher, Alex E.. Banner Sun Health Research Institute. The Longtine Center for Neurodegenerative Biochemistry; Estados Unidos
description The amyloid cascade hypothesis provides an economical mechanistic explanation for Alzheimer's disease (AD) dementia and correlated neuropathology. However, some nonagenarian individuals (high pathology controls, HPC) remain cognitively intact while enduring high amyloid plaque loads for decades. If amyloid accumulation is the prime instigator of neurotoxicity and dementia, specific protective mechanisms must enable these HPC to evade cognitive decline. We evaluated the neuropathological and biochemical differences existing between non-demented (ND)-HPC and an age-matched cohort with AD dementia. The ND-HPC selected for our study were clinically assessed as ND and possessed high amyloid plaque burdens. ELISA and Western blot analyses were used to quantify a group of proteins related to APP/Aβ/tau metabolism and other neurotrophic and inflammation-related molecules that have been found to be altered in neurodegenerative disorders and are pivotal to brain homeostasis and mental health. The molecules assumed to be critical in AD dementia, such as soluble or insoluble Aβ40, Aβ42 and tau were quantified by ELISA. Interestingly, only Aβ42 demonstrated a significant increase in ND-HPC when compared to the AD group. The vascular amyloid load which was not used in the selection of cases, was on the average almost 2-fold greater in AD than the ND-HPC, suggesting that a higher degree of microvascular dysfunction and perfusion compromise was present in the demented cohort. Neurofibrillary tangles were less frequent in the frontal cortices of ND-HPC. Biochemical findings included elevated vascular endothelial growth factor, apolipoprotein E and the neuroprotective factor S100B in ND-HPC, while anti-angiogenic pigment epithelium derived factor levels were lower. The lack of clear Aβ-related pathological/biochemical demarcation between AD and ND-HPC suggests that in addition to amyloid plaques other factors, such as neurofibrillary tangle density and vascular integrity, must play important roles in cognitive failure.
publishDate 2011
dc.date.none.fl_str_mv 2011
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/11336/13820
Maarouf, Chera L.; Daugs, Ian D.; Kokjohn, Tyler A.; Walker, Douglas G.; Hunter, Jesse M.; et al.; Alzheimer's disease and non-demented high pathology control nonagenarians: comparing and contrasting the biochemistry of cognitively successful aging; Public Library Of Science; Plos One; 6; 11; -1-2011; 1-17
1932-6203
url http://hdl.handle.net/11336/13820
identifier_str_mv Maarouf, Chera L.; Daugs, Ian D.; Kokjohn, Tyler A.; Walker, Douglas G.; Hunter, Jesse M.; et al.; Alzheimer's disease and non-demented high pathology control nonagenarians: comparing and contrasting the biochemistry of cognitively successful aging; Public Library Of Science; Plos One; 6; 11; -1-2011; 1-17
1932-6203
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0027291
info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0027291
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 Public Library Of Science
publisher.none.fl_str_mv Public Library Of Science
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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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
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