The Aggregation Paths and Products of Aβ42 Dimers Are Distinct from Those of the Aβ42 Monomer
(2016) In Biochemistry 55(44). p.6150-6161- Abstract
Extracts of Alzheimer's disease (AD) brain that contain what appear to be sodium dodecyl sulfate-stable amyloid β-protein (Aβ) dimers potently block LTP and impair memory consolidation. Brain-derived dimers can be physically separated the Aβ monomer, consist primarily of Aβ42, and resist denaturation by chaotropic agents. In nature, covalently cross-linked Aβ dimers could be generated in two ways: by the formation of a dityrosine (DiY) or an isopeptide ϵ-(γ-glutamyl)-lysine (Q-K) bond. We enzymatically cross-linked recombinant Aβ42 monomer to produce DiY and Q-K dimers and then used a range of biophysical methods to study their aggregation. Both Q-K and DiY dimers aggregate to form soluble assemblies distinct from the fibrillar... (More)
Extracts of Alzheimer's disease (AD) brain that contain what appear to be sodium dodecyl sulfate-stable amyloid β-protein (Aβ) dimers potently block LTP and impair memory consolidation. Brain-derived dimers can be physically separated the Aβ monomer, consist primarily of Aβ42, and resist denaturation by chaotropic agents. In nature, covalently cross-linked Aβ dimers could be generated in two ways: by the formation of a dityrosine (DiY) or an isopeptide ϵ-(γ-glutamyl)-lysine (Q-K) bond. We enzymatically cross-linked recombinant Aβ42 monomer to produce DiY and Q-K dimers and then used a range of biophysical methods to study their aggregation. Both Q-K and DiY dimers aggregate to form soluble assemblies distinct from the fibrillar aggregates formed by the Aβ monomer. The results suggest that the cross-links disfavor fibril formation from Aβ dimers, thereby enhancing the concentration of soluble aggregates akin to those in aqueous extracts of AD brain. Thus, it seems that Aβ dimers may play an important role in determining the formation of soluble rather than insoluble aggregates.
(Less)
- author
- O'Malley, Tiernan T. ; Witbold, William M. ; Linse, Sara LU and Walsh, Dominic M.
- organization
- publishing date
- 2016-11-08
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Biochemistry
- volume
- 55
- issue
- 44
- pages
- 12 pages
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- pmid:27750419
- wos:000387518900007
- scopus:84994753080
- ISSN
- 0006-2960
- DOI
- 10.1021/acs.biochem.6b00453
- language
- English
- LU publication?
- yes
- id
- 55db4fd6-359a-4531-a414-b228f0078f41
- date added to LUP
- 2016-11-29 08:35:43
- date last changed
- 2024-05-17 17:15:45
@article{55db4fd6-359a-4531-a414-b228f0078f41,
abstract = {{<p>Extracts of Alzheimer's disease (AD) brain that contain what appear to be sodium dodecyl sulfate-stable amyloid β-protein (Aβ) dimers potently block LTP and impair memory consolidation. Brain-derived dimers can be physically separated the Aβ monomer, consist primarily of Aβ42, and resist denaturation by chaotropic agents. In nature, covalently cross-linked Aβ dimers could be generated in two ways: by the formation of a dityrosine (DiY) or an isopeptide ϵ-(γ-glutamyl)-lysine (Q-K) bond. We enzymatically cross-linked recombinant Aβ42 monomer to produce DiY and Q-K dimers and then used a range of biophysical methods to study their aggregation. Both Q-K and DiY dimers aggregate to form soluble assemblies distinct from the fibrillar aggregates formed by the Aβ monomer. The results suggest that the cross-links disfavor fibril formation from Aβ dimers, thereby enhancing the concentration of soluble aggregates akin to those in aqueous extracts of AD brain. Thus, it seems that Aβ dimers may play an important role in determining the formation of soluble rather than insoluble aggregates.</p>}},
author = {{O'Malley, Tiernan T. and Witbold, William M. and Linse, Sara and Walsh, Dominic M.}},
issn = {{0006-2960}},
language = {{eng}},
month = {{11}},
number = {{44}},
pages = {{6150--6161}},
publisher = {{The American Chemical Society (ACS)}},
series = {{Biochemistry}},
title = {{The Aggregation Paths and Products of Aβ42 Dimers Are Distinct from Those of the Aβ42 Monomer}},
url = {{http://dx.doi.org/10.1021/acs.biochem.6b00453}},
doi = {{10.1021/acs.biochem.6b00453}},
volume = {{55}},
year = {{2016}},
}