The Pathogenic Aβ43 Is Enriched in Familial and Sporadic Alzheimer Disease

The amyloid-cascade hypothesis posits that the role of amyloid β-peptide (Aβ) in Alzheimer disease (AD) involves polymerization into structures that eventually are deposited as amyloid plaques. During this process, neurotoxic oligomers are formed that induce synaptic loss and neuronal death. Several...

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Main Authors:	Sandebring, Anna, Welander, Hedvig, Winblad, Bengt, Graff, Caroline, Tjernberg, Lars O.
Format:	Online
Language:	English
Published:	Public Library of Science 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3569467/

id	pubmed-3569467
recordtype	oai_dc
spelling	pubmed-35694672013-02-13 The Pathogenic Aβ43 Is Enriched in Familial and Sporadic Alzheimer Disease Sandebring, Anna Welander, Hedvig Winblad, Bengt Graff, Caroline Tjernberg, Lars O. Research Article The amyloid-cascade hypothesis posits that the role of amyloid β-peptide (Aβ) in Alzheimer disease (AD) involves polymerization into structures that eventually are deposited as amyloid plaques. During this process, neurotoxic oligomers are formed that induce synaptic loss and neuronal death. Several different isoforms of Aβ are produced, of which the 40 and 42 residue variants (Aβ40 and Aβ42) are the most common. Aβ42 has a strong tendency to form neurotoxic aggregates and is involved in AD pathogenesis. Longer Aβ isoforms, like the less studied Aβ43, are gaining attention for their higher propensity to aggregate into neurotoxic oligomers. To further investigate Aβ43 in AD, we conducted a quantitative study on Aβ43 levels in human brain. We homogenized human brain tissue and prepared fractions of various solubility; tris buffered saline (TBS), sodium dodecyl sulfate (SDS) and formic acid (FA). Levels of Aβ43, as well as Aβ40 and Aβ42, were quantified using ELISA. We compared quantitative data showing Aβ levels in occipital and frontal cortex from sporadic (SAD) and familial (FAD) AD cases, as well as non-demented (ND) controls. Results showed Aβ43 present in each fraction from the SAD and FAD cases, while its level was lower than the detection limit in the majority of the ND-cases. Aβ42 and Aβ43 were enriched in the less soluble fractions (SDS and FA) of SAD and FAD cases in both occipital and frontal cortex. Thus, although the total levels of Aβ43 in human brain are low compared to Aβ40 and Aβ42, we suggest that Aβ43 could initiate the formation of oligomers and amyloid plaques and thereby be crucial to AD pathogenesis. Public Library of Science 2013-02-11 /pmc/articles/PMC3569467/ /pubmed/23409063 http://dx.doi.org/10.1371/journal.pone.0055847 Text en © 2013 Sandebring et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Sandebring, Anna Welander, Hedvig Winblad, Bengt Graff, Caroline Tjernberg, Lars O.
spellingShingle	Sandebring, Anna Welander, Hedvig Winblad, Bengt Graff, Caroline Tjernberg, Lars O. The Pathogenic Aβ43 Is Enriched in Familial and Sporadic Alzheimer Disease
author_facet	Sandebring, Anna Welander, Hedvig Winblad, Bengt Graff, Caroline Tjernberg, Lars O.
author_sort	Sandebring, Anna
title	The Pathogenic Aβ43 Is Enriched in Familial and Sporadic Alzheimer Disease
title_short	The Pathogenic Aβ43 Is Enriched in Familial and Sporadic Alzheimer Disease
title_full	The Pathogenic Aβ43 Is Enriched in Familial and Sporadic Alzheimer Disease
title_fullStr	The Pathogenic Aβ43 Is Enriched in Familial and Sporadic Alzheimer Disease
title_full_unstemmed	The Pathogenic Aβ43 Is Enriched in Familial and Sporadic Alzheimer Disease
title_sort	pathogenic aβ43 is enriched in familial and sporadic alzheimer disease
description	The amyloid-cascade hypothesis posits that the role of amyloid β-peptide (Aβ) in Alzheimer disease (AD) involves polymerization into structures that eventually are deposited as amyloid plaques. During this process, neurotoxic oligomers are formed that induce synaptic loss and neuronal death. Several different isoforms of Aβ are produced, of which the 40 and 42 residue variants (Aβ40 and Aβ42) are the most common. Aβ42 has a strong tendency to form neurotoxic aggregates and is involved in AD pathogenesis. Longer Aβ isoforms, like the less studied Aβ43, are gaining attention for their higher propensity to aggregate into neurotoxic oligomers. To further investigate Aβ43 in AD, we conducted a quantitative study on Aβ43 levels in human brain. We homogenized human brain tissue and prepared fractions of various solubility; tris buffered saline (TBS), sodium dodecyl sulfate (SDS) and formic acid (FA). Levels of Aβ43, as well as Aβ40 and Aβ42, were quantified using ELISA. We compared quantitative data showing Aβ levels in occipital and frontal cortex from sporadic (SAD) and familial (FAD) AD cases, as well as non-demented (ND) controls. Results showed Aβ43 present in each fraction from the SAD and FAD cases, while its level was lower than the detection limit in the majority of the ND-cases. Aβ42 and Aβ43 were enriched in the less soluble fractions (SDS and FA) of SAD and FAD cases in both occipital and frontal cortex. Thus, although the total levels of Aβ43 in human brain are low compared to Aβ40 and Aβ42, we suggest that Aβ43 could initiate the formation of oligomers and amyloid plaques and thereby be crucial to AD pathogenesis.
publisher	Public Library of Science
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3569467/
_version_	1611953959280312320

The Pathogenic Aβ43 Is Enriched in Familial and Sporadic Alzheimer Disease

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