The Caenorhabditis elegans A beta 1-42 model of Alzheimer disease predominantly expresses A beta 3-42

Gawain McColl, Blaine R Roberts, Adam P Gunn, Keyla A Perez, Deborah J Tew, Colin L Masters, Kevin J Barnham, Robert A Cherny, Ashley I Bush

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Abstract

Transgenic expression of human amyloid beta (A beta) peptide in body wall muscle cells of Caenorhabditis elegans has been used to better understand aspects of Alzheimer disease (AD). In human aging and AD, A beta undergoes post-translational changes including covalent modifications, truncations, and oligomerization. Amino truncated A beta is increasingly recognized as potentially contributing to AD pathogenesis. Here we describe surface-enhanced laser desorption ionization-time of flight mass spectrometry mass spectrometry of A beta peptide in established transgenic C. elegans lines. Surprisingly, the A beta being expressed is not full-length 1-42 (amino acids) as expected but rather a 3-42 truncation product. In vitro analysis demonstrates that A beta(3-42) self-aggregates like A beta(1-42), but more rapidly, and forms fibrillar structures. Similarly, A beta(3-42) is also the more potent initiator of A beta(1-40) aggregation. Seeded aggregation via A beta(3-42) is further enhanced via co-incubation with the transition metal Cu(II). Although unexpected, the C. elegans model of A beta expression can now be co-opted to study the proteotoxic effects and processing of A beta(3-42).

Original languageEnglish
Pages (from-to)22697-702
Number of pages6
JournalThe Journal of Biological Chemistry
Volume284
Issue number34
DOIs
Publication statusPublished - 21 Aug 2009
Externally publishedYes

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McColl, G., Roberts, B. R., Gunn, A. P., Perez, K. A., Tew, D. J., Masters, C. L., ... Bush, A. I. (2009). The Caenorhabditis elegans A beta 1-42 model of Alzheimer disease predominantly expresses A beta 3-42. The Journal of Biological Chemistry, 284(34), 22697-702. https://doi.org/10.1074/jbc.C109.028514