Label-Free Detection and Self-Aggregation of Amyloid β‑Peptides Based on Plasmonic Effects Induced by Ag Nanoparticles: Implications in Alzheimer’s Disease Diagnosis

Plasmon-assisted effects were used in this work to study the dynamical behavior of amyloid β peptides (Aβ), in particular Aβ(25–35), on silver nanoparticles. Amyloid peptides derive from the proteolytic cleavage of the glycoprotein named amyloid precursor protein (APP). Aβ(25–35) represents the sequence that concentrates the biological active region of all of the amyloid peptide family, being the shortest fragment of Aβ that retains the toxicity of the full length. The plasmon effects employed in this work were the localized surface plasmon resonance (LSPR), the plasmon hybridization resulting from plasmonic NPs aggregation, and the enhancement of electric field leading to the so-called surface-enhanced Raman scattering (SERS) spectroscopy on nanostructures. While LSPR and plasmon hybridization of nanoparticles are highly sensitive to adsorption and dynamical processes undergone by these peptides on the metal surface, direct nonlabeled SERS spectra provided valuable information regarding the secondary structure of peptides. Specifically, SERS revealed the interaction mechanism of peptides with the metal and the structural rearrangement processes involved in the self-aggregation leading to fibrillation. These effects were also followed at different peptide concentrations. Plasmon resonance and SERS results were obtained with transmission electron microscopy (TEM) images that also corroborated the self-aggregation processes undergone by these peptides leading to the formation of supramolecular aggregates at different concentrations. Nanospheres and protofibrils formed in the first stages of the amyloid assembly were identified by TEM. The physicochemical information provided by this work will be of great importance to design plasmon-based nanoplatforms for simultaneous amyloid detection and structural characterization. Furthermore, these platforms have promising applications in the detection of Alzheimer’s disease and its treatment based on the bioaccumulation of these toxic peptides on NPs, where they can be trapped and removed from biological systems, thus reducing their neurotoxicity.