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Alzheimer's Research & Therapy
Published in: Alzheimer's Research & Therapy 3/2012

Open Access 01-06-2012 | Research

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

Authors: Brenda D Moore, Paramita Chakrabarty, Yona Levites, Tom L Kukar, Ann-Marie Baine, Tina Moroni, Thomas B Ladd, Pritam Das, Dennis W Dickson, Todd E Golde

Published in: Alzheimer's Research & Therapy | Issue 3/2012

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Abstract

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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Metadata
Title
Overlapping profiles of Aβ peptides in the Alzheimer's disease and pathological aging brains
Authors
Brenda D Moore
Paramita Chakrabarty
Yona Levites
Tom L Kukar
Ann-Marie Baine
Tina Moroni
Thomas B Ladd
Pritam Das
Dennis W Dickson
Todd E Golde
Publication date
01-06-2012
Publisher
BioMed Central
Published in
Alzheimer's Research & Therapy / Issue 3/2012
Electronic ISSN: 1758-9193
DOI
https://doi.org/10.1186/alzrt121

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