Electrochemical Fingerprinting for Discrimination of $\mathrm{A}\beta_{3-16}, \mathrm{A}\beta_{11-16}$ and their Pyroglutamate Counterparts, Related to Alzheimer's Disease

The $\beta$-amyloid $(\mathrm{A}\beta)$ peptides are believed to be crucial for Alzheimer's disease (AD) by forming toxic oligomers in the brain, which cause neuronal death. Consequently, these peptides serve as biomarkers of AD. Various forms of AP have been identified so far, and their levels vary between healthy and afflicted individuals. Moreover, forms naturally modified through pyroglutamylation at the amino terminus are characterized by higher toxicity and resistance to proteolytic degradation. The current methods focus exclusively on the determination of the $\mathrm{A}\beta_{1-42}/\mathrm{A}\beta_{1-40}$ ratio, losing information on the broad spectrum of other forms, which could be at least as important as the routinely determined AP peptides. In this work, we proposed a novel detection strategy of short analogs of AP peptides: $\mathrm{A}\beta_{3-16}$, APll-16, and their pyroglutamate counterparts related to Alzheimer's disease. The proposed approach is based on the chemometric analysis of voltammetric signals recorded in solutions of Cu(II)-A $\beta$ complexes for generating and extracting characteristic fingerprints of the different $\mathrm{A}\beta$ analogs for their further discrimination.