Alzheimer's biomarkers inspected through Raman-based nano-strategies

The elusive nature of misfolded peptides and aggregates of proteins involved in neurodegenerative disorders such as Alzheimer's and Parkinson's represents the main failure cause of any clinical trial attempted so far. Current research is extensively devoting efforts in unravelling the basis of the disease onset including the formation mechanism of aberrant protein species and the extreme structural variability in their toxic intermediates [1]. Raman and Surface enhanced Raman spectroscopy (SERS) are powerful tools for structural characterization and detection of biomolecular species present in traces in liquid environments including complex body fluids. These techniques can synergistically reveal peculiar structural features such as elements of secondary structures and characteristic surface-exposed residues in different peptide conformations, which can play a primary role in ruling intra- and inter-molecular interactions in a neuronal environment. Herein plasmonic optofluidic platforms of finely shaped silver nanoparticles are designed and fabricated with the aim of setting up SERS systems for label-free direct detection and analysis of proteins and oligomers associated with Alzheimer's disease. Silver nanocubes and silver nanowires are synthesized and assembled through controlled methods to build up 2D patterned nanostructures with intense SERS activity [2,3]. By means of tunable dewetting and confined drop evaporation processes, the interaction pathways between the SERS active area and the analyte is properly addressed to enrich the hot spot regions of the system with the target molecules in turn improving effectiveness and sensitivity. Beyond a sensible and reproducible detection of various model and real biomolecular species these SERS platforms allow an accurate structural analysis of toxic oligomers of beta-amyloid, which are recognized among the main biomarkers of the Alzheimer's pathology. [1] C. D'Andrea et al., Small 2018, 14, 1800890. [2] M. Banchelli et al., Sci. Rep. 2018, 8, 1033. [3] M.Banchelli et al., ChemNanoMat 2019, 5, 1.