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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/13820
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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) |
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 |
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1844613306716782592 |
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13.070432 |