Pyroglutamate-Aβ: role in the natural history of Alzheimer's disease.

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.

• 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)
• Copyright: Copyright © 2010 Elsevier Ltd. All rights reserved.

Chemical References

• Amyloid beta-Peptides
• Amyloid beta-Protein Precursor
• Pyrrolidonecarboxylic Acid

Topics

• Alzheimer Disease (metabolism, pathology)
• Amyloid beta-Peptides (metabolism)
• Amyloid beta-Protein Precursor (metabolism)
• Animals
• Humans
• Mice
• Pyrrolidonecarboxylic Acid (metabolism)