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

Adam P Gunn, Colin L Masters, Robert A Cherny

Research output: Contribution to journalReview article

47 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1915-1918
Number of pages4
JournalInternational Journal of Biochemistry and Cell Biology
Volume42
Issue number12
DOIs
Publication statusPublished - Dec 2010
Externally publishedYes

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