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Overlapping profiles of Aβ peptides in the Alzheimer's disease and pathological aging brains

INTRODUCTION: A hallmark of Alzheimer's disease (AD) is the presence of senile plaques composed of aggregated amyloid β (Aβ) peptides. Pathological aging (PA) is a postmortem classification that has been used to describe brains with plaque pathology similar in extent to AD, minimal cortical tau...

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Autores principales: Moore, Brenda D, Chakrabarty, Paramita, Levites, Yona, Kukar, Tom L, Baine, Ann-Marie, Moroni, Tina, Ladd, Thomas B, Das, Pritam, Dickson, Dennis W, Golde, Todd E
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3506932/
https://www.ncbi.nlm.nih.gov/pubmed/22621179
http://dx.doi.org/10.1186/alzrt121
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author Moore, Brenda D
Chakrabarty, Paramita
Levites, Yona
Kukar, Tom L
Baine, Ann-Marie
Moroni, Tina
Ladd, Thomas B
Das, Pritam
Dickson, Dennis W
Golde, Todd E
author_facet Moore, Brenda D
Chakrabarty, Paramita
Levites, Yona
Kukar, Tom L
Baine, Ann-Marie
Moroni, Tina
Ladd, Thomas B
Das, Pritam
Dickson, Dennis W
Golde, Todd E
author_sort Moore, Brenda D
collection PubMed
description INTRODUCTION: A hallmark of Alzheimer's disease (AD) is the presence of senile plaques composed of aggregated amyloid β (Aβ) peptides. Pathological aging (PA) is a postmortem classification that has been used to describe brains with plaque pathology similar in extent to AD, minimal cortical tau pathology, and no accompanying history of cognitive decline in the brain donor prior to death. PA may represent either a prodromal phase of AD, a benign form of Aβ accumulation, or inherent individual resistance to the toxic effects of Aβ accumulation. To attempt to distinguish between these possibilities we have systematically characterized Aβ peptides in a postmortem series of PA, AD and non-demented control (NDC) brains. METHODS: Aβ was sequentially extracted with tris buffered saline (TBS), radioimmunoprecipitation buffer (RIPA), 2% sodium dodecyl sulfate (SDS) and 70% formic acid (FA) from the pre-frontal cortex of 16 AD, eight PA, and six NDC patients. These extracts were analyzed by 1) a panel of Aβ sandwich ELISAs, 2) immunoprecipitation followed by mass spectrometry (IP/MS) and 3) western blotting. These studies enabled us to asses Aβ levels and solubility, peptide profiles and oligomeric assemblies. RESULTS: In almost all extracts (TBS, RIPA, 2% SDS and 70% FA) the average levels of Aβ1-40, Aβ1-42, Aβ total, and Aβx-42 were greatest in AD. On average, levels were slightly lower in PA, and there was extensive overlap between Aβ levels in individual PA and AD cases. The profiles of Aβ peptides detected using IP/MS techniques also showed extensive similarity between the PA and AD brain extracts. In select AD brain extracts, we detected more amino-terminally truncated Aβ peptides compared to PA patients, but these peptides represented a minor portion of the Aβ observed. No consistent differences in the Aβ assemblies were observed by western blotting in the PA and AD groups. CONCLUSIONS: We found extensive overlap with only subtle quantitative differences between Aβ levels, peptide profiles, solubility, and SDS-stable oligomeric assemblies in the PA and AD brains. These cross-sectional data indicate that Aβ accumulation in PA and AD is remarkably similar. Such data would be consistent with PA representing a prodromal stage of AD or a resistance to the toxic effects of Aβ.
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spelling pubmed-35069322012-11-28 Overlapping profiles of Aβ peptides in the Alzheimer's disease and pathological aging brains Moore, Brenda D Chakrabarty, Paramita Levites, Yona Kukar, Tom L Baine, Ann-Marie Moroni, Tina Ladd, Thomas B Das, Pritam Dickson, Dennis W Golde, Todd E Alzheimers Res Ther Research INTRODUCTION: A hallmark of Alzheimer's disease (AD) is the presence of senile plaques composed of aggregated amyloid β (Aβ) peptides. Pathological aging (PA) is a postmortem classification that has been used to describe brains with plaque pathology similar in extent to AD, minimal cortical tau pathology, and no accompanying history of cognitive decline in the brain donor prior to death. PA may represent either a prodromal phase of AD, a benign form of Aβ accumulation, or inherent individual resistance to the toxic effects of Aβ accumulation. To attempt to distinguish between these possibilities we have systematically characterized Aβ peptides in a postmortem series of PA, AD and non-demented control (NDC) brains. METHODS: Aβ was sequentially extracted with tris buffered saline (TBS), radioimmunoprecipitation buffer (RIPA), 2% sodium dodecyl sulfate (SDS) and 70% formic acid (FA) from the pre-frontal cortex of 16 AD, eight PA, and six NDC patients. These extracts were analyzed by 1) a panel of Aβ sandwich ELISAs, 2) immunoprecipitation followed by mass spectrometry (IP/MS) and 3) western blotting. These studies enabled us to asses Aβ levels and solubility, peptide profiles and oligomeric assemblies. RESULTS: In almost all extracts (TBS, RIPA, 2% SDS and 70% FA) the average levels of Aβ1-40, Aβ1-42, Aβ total, and Aβx-42 were greatest in AD. On average, levels were slightly lower in PA, and there was extensive overlap between Aβ levels in individual PA and AD cases. The profiles of Aβ peptides detected using IP/MS techniques also showed extensive similarity between the PA and AD brain extracts. In select AD brain extracts, we detected more amino-terminally truncated Aβ peptides compared to PA patients, but these peptides represented a minor portion of the Aβ observed. No consistent differences in the Aβ assemblies were observed by western blotting in the PA and AD groups. CONCLUSIONS: We found extensive overlap with only subtle quantitative differences between Aβ levels, peptide profiles, solubility, and SDS-stable oligomeric assemblies in the PA and AD brains. These cross-sectional data indicate that Aβ accumulation in PA and AD is remarkably similar. Such data would be consistent with PA representing a prodromal stage of AD or a resistance to the toxic effects of Aβ. BioMed Central 2012-05-23 /pmc/articles/PMC3506932/ /pubmed/22621179 http://dx.doi.org/10.1186/alzrt121 Text en Copyright ©2012 Moore et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Moore, Brenda D
Chakrabarty, Paramita
Levites, Yona
Kukar, Tom L
Baine, Ann-Marie
Moroni, Tina
Ladd, Thomas B
Das, Pritam
Dickson, Dennis W
Golde, Todd E
Overlapping profiles of Aβ peptides in the Alzheimer's disease and pathological aging brains
title Overlapping profiles of Aβ peptides in the Alzheimer's disease and pathological aging brains
title_full Overlapping profiles of Aβ peptides in the Alzheimer's disease and pathological aging brains
title_fullStr Overlapping profiles of Aβ peptides in the Alzheimer's disease and pathological aging brains
title_full_unstemmed Overlapping profiles of Aβ peptides in the Alzheimer's disease and pathological aging brains
title_short Overlapping profiles of Aβ peptides in the Alzheimer's disease and pathological aging brains
title_sort overlapping profiles of aβ peptides in the alzheimer's disease and pathological aging brains
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3506932/
https://www.ncbi.nlm.nih.gov/pubmed/22621179
http://dx.doi.org/10.1186/alzrt121
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