A beta dimers differ from monomers in structural propensity, aggregation paths and population of synaptotoxic assemblies
(2014) In Biochemical Journal 461. p.413-426- Abstract
- Dimers of A beta (amyloid beta-protein) are believed to play an important role in Alzheimer's disease. In the absence of sufficient brain-derived dimers, we studied one of the only possible dimers that could be produced in vivo, [A beta](DiY) (dityrosine cross-linked A beta). For comparison, we used the A beta monomer and a design dimer cross-linked by replacement of Ser(26) with cystine [A beta S26C](2). We showed that similar to monomers, unaggregated dimers lack appreciable structure and fail to alter long-term potentiation. Importantly, dimers exhibit subtly different structural propensities from monomers and each other, and can self-associate to form larger assemblies. Although [A beta](DiY) and [A beta S26C](2) have distinct... (More)
- Dimers of A beta (amyloid beta-protein) are believed to play an important role in Alzheimer's disease. In the absence of sufficient brain-derived dimers, we studied one of the only possible dimers that could be produced in vivo, [A beta](DiY) (dityrosine cross-linked A beta). For comparison, we used the A beta monomer and a design dimer cross-linked by replacement of Ser(26) with cystine [A beta S26C](2). We showed that similar to monomers, unaggregated dimers lack appreciable structure and fail to alter long-term potentiation. Importantly, dimers exhibit subtly different structural propensities from monomers and each other, and can self-associate to form larger assemblies. Although [A beta](DiY) and [A beta S26C](2) have distinct aggregation pathways, they both populate bioactive soluble assemblies for longer durations than A beta monomers. Our results indicate that the link between A beta dimers and Alzheimer's disease results from the ability of dimers to further assemble and form synaptotoxic assemblies that persist for long periods of time. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4591816
- author
- O'Malley, Tiernan T. ; Oktaviani, Nur Alia ; Zhang, Dainan ; Lomakin, Aleksey ; O'Nuallain, Brian ; Linse, Sara LU ; Benedek, George B. ; Rowan, Michael J. ; Mulder, Frans A. A. and Walsh, Dominic M.
- organization
- publishing date
- 2014
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Alzheimer's disease, amyloid beta-protein, long-term potentiation, nuclear magnetic resonance (NMR), synaptic plasticity
- in
- Biochemical Journal
- volume
- 461
- pages
- 413 - 426
- publisher
- Portland Press
- external identifiers
-
- wos:000339126600006
- scopus:84903174803
- pmid:24785004
- ISSN
- 0264-6021
- DOI
- 10.1042/BJ20140219
- language
- English
- LU publication?
- yes
- id
- e1040e99-d4fd-43f5-8d05-e22a0ff183c6 (old id 4591816)
- date added to LUP
- 2016-04-01 14:33:11
- date last changed
- 2022-05-20 01:04:36
@article{e1040e99-d4fd-43f5-8d05-e22a0ff183c6,
abstract = {{Dimers of A beta (amyloid beta-protein) are believed to play an important role in Alzheimer's disease. In the absence of sufficient brain-derived dimers, we studied one of the only possible dimers that could be produced in vivo, [A beta](DiY) (dityrosine cross-linked A beta). For comparison, we used the A beta monomer and a design dimer cross-linked by replacement of Ser(26) with cystine [A beta S26C](2). We showed that similar to monomers, unaggregated dimers lack appreciable structure and fail to alter long-term potentiation. Importantly, dimers exhibit subtly different structural propensities from monomers and each other, and can self-associate to form larger assemblies. Although [A beta](DiY) and [A beta S26C](2) have distinct aggregation pathways, they both populate bioactive soluble assemblies for longer durations than A beta monomers. Our results indicate that the link between A beta dimers and Alzheimer's disease results from the ability of dimers to further assemble and form synaptotoxic assemblies that persist for long periods of time.}},
author = {{O'Malley, Tiernan T. and Oktaviani, Nur Alia and Zhang, Dainan and Lomakin, Aleksey and O'Nuallain, Brian and Linse, Sara and Benedek, George B. and Rowan, Michael J. and Mulder, Frans A. A. and Walsh, Dominic M.}},
issn = {{0264-6021}},
keywords = {{Alzheimer's disease; amyloid beta-protein; long-term potentiation; nuclear magnetic resonance (NMR); synaptic plasticity}},
language = {{eng}},
pages = {{413--426}},
publisher = {{Portland Press}},
series = {{Biochemical Journal}},
title = {{A beta dimers differ from monomers in structural propensity, aggregation paths and population of synaptotoxic assemblies}},
url = {{http://dx.doi.org/10.1042/BJ20140219}},
doi = {{10.1042/BJ20140219}},
volume = {{461}},
year = {{2014}},
}