Electrochemical Oxidation of Benzothiazole Dyes for Monitoring Amyloid Formation Related to the Alzheimer’s Disease
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".