Simultaneous Detection of Tyrosine and Structure‐Specific Intrinsic Fluorescence in the Fibrillation of Alzheimer's Associated Peptides

Abstract

Understanding of the structural changes during their aggregation and interaction is a prerequisite for establishing the precise clinical relevance of human islet amyloid polypeptide (hIAPP) (involved in Type-II Diabetes Mellitus) in the treatment of Alzheimer's disease stemmed from beta-amyloid (Aβ). Herein, we show that the steady-state emission spectra obtained from photoluminescence (PL) simultaneously capture both the tyrosine derivative (tyrosinate) and the structure-specific intrinsic fluorescence during the aggregation of Aβ and hIAPP. We observe multiple peaks in the emission spectra which exist for structure-specific intrinsic fluorescence, and use the second derivative UV-Vis spectra and the shift in the tyrosine peak as a quantitative measure of the dissimilitude in the electronic states and the fibril growth. We further applied these techniques to detect the static electric field (0, 40, 120, 200 V/cm) induced promotion and inhibition of fibrillation in Aβ, hIAPP and their electric field dependent role in the fibrillation of Aβ : hIAPP(1 : 1). The results were corroborated by field-emission scanning electron microscopy (FESEM), and the determinations of secondary structures by Fourier transform infrared spectroscopy (FTIR). The results indicate that the emission spectrum can be used as a sensor to detect the presence of fibrils; hence for screening potential inhibitors of amyloid fibrillation.

Alzheimer’s Disease Biomarker Detection Using Field Effect Transistor-Based Biosensor

“…As aforementioned, Aβ and tau are two key biomarkers widely approved and extensively studied. The presence of electroactive groups, such as tyrosine, histidine, and methionine, in the Aβ structure enables the detection of this biomarker by recognizing oxidized peaks at ~0.6 V and 1.5 V, and waves at 1-1.5 V, respectively [109,112,113]. However, this approach is non-specific.…”

SAM-Support-Based Electrochemical Sensor for Aβ Biomarker Detection of Alzheimer’s Disease

“…Many studies have demonstrated that Aβ can be completely detected by employing an electrochemical sensor to obtain a low LOD at picograms or femtograms per milliliter [ 53 , 63 , 64 , 67 , 69 , 70 , 71 , 82 ]. The Aβ peptide structure has a tyrosine group, histidine, and methionine which participate in the redox reaction with an oxidized peak at ~0.6 and ~1.05 and wave at 1–1.5 V vs. Ag/AgCl on a carbon surface [ 83 , 84 ]. The oxidation occurring on the residual groups under a supplied voltage indicates the detection ability for Aβ biomarkers; however, this method detects a plethora of other proteins containing such groups as well.…”

Electric-field induced modulation of amorphous protein aggregates: polarization, deformation, and reorientation

“…Note that only relatively weak electric fields (a few V/mm) are required to affect the amorphous aggregates in comparison to those used to alter protein secondary structure and promote fibril formation 54,55 . The reason for this might be the weak inter-protein interaction within the amorphous aggregates.…”