Engineering Nanoplatforms for Alzheimer's Disease Detection via Biomolecular Corona Proteomic and Lipidomic Profiling

The escalating global prevalence of Alzheimer's disease (AD) requires the development of sensitive, non-invasive diagnostic strategies capable of detecting pathological changes previous the clinical onset. By exploiting the spontaneous formation of the biomolecular corona (BC) around nanoparticles (NPs), it's possible to capture a rich, disease-specific fingerprint from the plasma that reflects systemic alterations often invisible to traditional diagnostic assays. In the present study, we demonstrate the efficacy of an innovative nanotechnological platform utilizing a synergistic dual-silica NPs system (comprising amino- and sulfonate-functionalized surfaces) integrated with proteomic and lipidomic profiling of the NP-associated BC. Our results revealed a significant enrichment of ribosomal machinery in the BC of AD patients, contrasted by a simultaneous decrease of glycolytic enzymes and mitochondrial respiratory components. This metabolic impairment is further corroborated by the lipidomic profile, which shows a reduction in short-chain acyl-carnitines (C2, C3, C5) and essential membrane phospholipids. Additionally, the observed loss of structural proteins, such as Cofilin-1 and Vinculin, contributes to a comprehensive molecular fingerprint unique to the AD phenotype.