Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 127, Issue 7, Pages 2075-2084Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ja044531p
Keywords
-
Categories
Funding
- NIA NIH HHS [AG18921] Funding Source: Medline
- NINDS NIH HHS [NS44147, NS38328] Funding Source: Medline
Ask authors/readers for more resources
The amyloid beta-protein (Abeta) is a seminal neuropathic agent in Alzheimer's disease (AD). Recent evidence points to soluble Abeta oligomers as the probable neurotoxic species. Among the naturally occurring Abeta peptides, the 42-residue form Abeta42 is linked particularly strongly with AD, even though it is produced at approximately 10% of the levels of the more abundant 40-residue form Abeta40. Here, we apply mass spectrometry and ion mobility to the study of Abeta42 and its Pro(19) alloform. The Phe(19) --> Pro(19) substitution blocks fibril formation by [Pro(19)]Abeta42. Evidence indicates that solution-like structures of Abeta monomers are electrosprayed and characterized. Unfiltered solutions of Abeta42 produce only monomers and large oligomers, whereas [Pro(19)]Abeta42 solutions produce abundant monomers, dinners, trimers, and tetramers; but no large oligomers. When passed through a 10,000 amu filter and immediately sampled, Abeta42 solutions produce monomers, dimers, tetramers, hexamers, and an aggregate of two hexamers that may be the first step in protofibril formation. These results are consistent with recently published photochemical cross-linking data and lend support to recent aggregation mechanisms proposed by Bitan, Teplow, and co-workers [J. Biol. Chem. 2003, 278, 34882-34889].
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available