Abstract |
The accumulation of amyloid-beta (Aβ) peptides is believed to be a central contributor to the neurodegeneration typically seen in Alzheimer's disease (AD) brain. Aβ extracted from AD brains invariably possesses extensive truncations, yielding peptides of differing N- and C-terminal composition. Whilst Aβ is often abundant in the brains of cognitively normal elderly people, the brains of AD patients are highly enriched for N-terminally truncated Aβ bearing the pyroglutamate modification. Pyroglutamate-Aβ (pE-Aβ) has a higher propensity for oligomerisation and aggregation than full-length Aβ, potentially seeding the accumulation of neurotoxic Aβ oligomers and amyloid deposits. In addition, pE-Aβ has increased resistance to clearance by peptidases, causing these peptides to persist in biological fluids and tissues. The extensive deposition of pE-Aβ in human AD brain is under-represented in many transgenic mouse models of AD, reflecting major differences in the production and processing of Aβ peptides in these models compared to the human disease state.
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Authors | Adam P Gunn, Colin L Masters, Robert A Cherny |
Journal | The international journal of biochemistry & cell biology
(Int J Biochem Cell Biol)
Vol. 42
Issue 12
Pg. 1915-8
(Dec 2010)
ISSN: 1878-5875 [Electronic] Netherlands |
PMID | 20833262
(Publication Type: Journal Article, Review)
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Copyright | Copyright © 2010 Elsevier Ltd. All rights reserved. |
Chemical References |
- Amyloid beta-Peptides
- Amyloid beta-Protein Precursor
- Pyrrolidonecarboxylic Acid
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Topics |
- Alzheimer Disease
(metabolism, pathology)
- Amyloid beta-Peptides
(metabolism)
- Amyloid beta-Protein Precursor
(metabolism)
- Animals
- Humans
- Mice
- Pyrrolidonecarboxylic Acid
(metabolism)
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