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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3569467?pdf=render |
| _version_ | 1811236550791397376 |
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| author | Anna Sandebring Hedvig Welander Bengt Winblad Caroline Graff Lars O Tjernberg |
| author_facet | Anna Sandebring Hedvig Welander Bengt Winblad Caroline Graff Lars O Tjernberg |
| author_sort | Anna Sandebring |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T12:10:07Z |
| format | Article |
| id | doaj.art-6437bc5d52a94192bec3dab68b3fe0d6 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T12:10:07Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-6437bc5d52a94192bec3dab68b3fe0d62022-12-22T03:33:36ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0182e5584710.1371/journal.pone.0055847The pathogenic aβ43 is enriched in familial and sporadic Alzheimer disease.Anna SandebringHedvig WelanderBengt WinbladCaroline GraffLars O TjernbergThe 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.http://europepmc.org/articles/PMC3569467?pdf=render |
| spellingShingle | Anna Sandebring Hedvig Welander Bengt Winblad Caroline Graff Lars O Tjernberg The pathogenic aβ43 is enriched in familial and sporadic Alzheimer disease. PLoS ONE |
| title | 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_short | The pathogenic aβ43 is enriched in familial and sporadic Alzheimer disease. |
| title_sort | pathogenic aβ43 is enriched in familial and sporadic alzheimer disease |
| url | http://europepmc.org/articles/PMC3569467?pdf=render |
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