Electrochemical oxidation of benzothiazole dyes for monitoring amyloid formation related to the Alzheimer's disease.
Alzheimer's disease (AD) is associated with the formation and deposition of amyloid fibrils. A better understanding of the oligomeric intermediates on the pathway to fibrilization is highly desired, but efficient methods for their detection are lacking. We have studied the interfacial properties of amyloid peptides (Abeta-40 and Abeta-42) and the course of their aggregation in vitro in the presence of the benzothiazole dyes Thioflavin T (4-(3,6-dimethyl-1,3-benzothiazol-3-ium-2-yl)-N,N-dimethylaniline) chloride, ThT) and BTA-1 ([2-(4'-(methylamino)phenyl) benzothiazole]) using electrochemical techniques. The intercalative properties of these dyes between the beta-sheets of amyloids have been well-documented using fluorescence-based systems, but their electrochemistry is reported here for the first time. ThT is positively charged and water-soluble, whereas BTA-1 is neutral and hydrophobic. Immediate and significantly different electrochemical characteristics of these dyes were observed in the presence of amyloid peptides. A decrease of the BTA-1 oxidation signal was observed upon incubation with Abeta-40. Incubation of BTA-1 with Abeta-42 results in an increased rate of exponential decay, which was in agreement with the known rapid aggregation properties of Abeta-42. The aggregation of amyloid peptides with ThT resulted in an unexpected increase in signal after 24 h of incubation, consistent for both peptides. The results of the electrochemical trials were confirmed using simultaneous fluorescence analysis of the same incubated amyloid samples. The very early changes in the interfacial behavior of the amyloid peptides after the first few minutes of incubation were attributed to the fast oligomerization of the peptides with the disruption of the intercalative properties of the benzothiazole dyes between the beta-sheets. The subsequent changes in the electrochemical signals can be related to the onset of intercalation between the fibrils. Our results demonstrate the utility of electrochemical oxidation signals of the benzothiazole dyes as a new and simple tool for the investigation of amyloid formation related to the AD.
Veloso
Anthony Joseph
AJ
Department of Physical and Environmental Sciences, University of Toronto at Scarborough, 1265 Military Trail, Toronto M1C 1A4, ON, Canada.
Hung
Vinci Wing Sze
VW
Sindhu
Guneet
G
Constantinof
Andrea
A
Kerman
Kagan
K
D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000096:biosynthesis* / Q000737:chemistry; D052160:Benzothiazoles / Q000737:chemistry*; D055664:Electrochemical Techniques / Q000379:methods*; D006801:Humans; D010084:Oxidation-Reduction
D016229:Amyloid beta-Peptides; D052160:Benzothiazoles