Abeta-polyacrolein aggregates: novel mechanism of plastic formation in senile plaques.
High levels of acrolein (H2C=HC-CH=O) occur in Alzheimer's brain. Amyloid-beta (Abeta) peptide co-localizes with acrolein presumably due to Abeta-induced lipid peroxidation. Focal production of acrolein may yield a transient elevation in the concentration of acrolein that may be susceptible to polymerization via basic latex polymer chemistry. Following incubation of Abeta with acrolein (16-750 mM), we observed the formation of thin plastic fragments that were extensively punctuated. Planar aggregates stained for protein and for cross-beta structures suggesting an Abeta-polyacrolein colloidal mixture. Depending on acrolein concentration and incubation time, we observed uniformly sized planar aggregates (approximately 10 microm2) or monolayers (>100 mm2) of thin polyacrolein films embedded with Abeta oligomers. The ability of Abeta to catalyze the polymerization of acrolein is likely due to Abeta's surfactant and redox properties. These observations suggest that plastic in the form of Abeta-polyacrolein latexes may exist in neural tissue contributing to the pathogenesis of Alzheimer's disease.
Seidler
Norbert W
NW
Kansas City University of Medicine and Biosciences, Department of Biochemistry, 1750 Independence Avenue, Kansas City, MO 64106, USA. nseidler@kcumb.edu
Squire
Trevor J
TJ
D000171:Acrolein / Q000737:chemistry*; D000544:Alzheimer Disease; D000682:Amyloid / Q000737:chemistry; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D001703:Biophysics / Q000379:methods; D001704:Biopolymers / Q000737:chemistry; D001921:Brain / Q000378:metabolism; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D058225:Plaque, Amyloid / Q000737:chemistry*; D010969:Plastics; D011108:Polymers / Q000737:chemistry*; D013997:Time Factors
D000682:Amyloid; D016229:Amyloid beta-Peptides; D001704:Biopolymers; D010446:Peptide Fragments; D010455:Peptides; D010969:Plastics; D011108:Polymers; C029975:polyacrolein; D000171:Acrolein