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

Int J Biochem Cell Biol. 2010 Dec;42(12):1915-8. doi: 10.1016/j.biocel.2010.08.015. Epub 2010 Sep 15.


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.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Humans
  • Mice
  • Pyrrolidonecarboxylic Acid / metabolism*


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