Abstract

Alzheimer's disease (AD), one of the most common neurodegenerative disorders among the elderly, poses significant challenges due to limited therapeutic options and diagnostic complexity. The soluble and insoluble forms of ?-amyloid (A?) peptide serve as disease biomarkers present in the early stages of the disease, highlighting the importance of developing detection methodologies. We designed a nanosystem utilizing silica-coated plasmonic nanoparticles linked to a CRANAD probe (AuNRs@SiO2-CR2), which shows an improved fluorescence signal for the detection of A? through a surface enhancement effect. Our study identified an optimal thickness of the silica layer that results in enhanced fluorescence intensity. Furthermore, we observed a notable preferential detection towards the more toxic soluble A? species. In comparison to the free CRANAD, we achieved an approximately 800-fold increase in fluorescence signal, hence facilitating an improvement of the sensitivity for the detection of the A? aggregates. The designed nanomaterials will enhance the detection of soluble A? aggregates, which is crucial for the early diagnosis of Alzheimer´s disease. © 2025 Elsevier B.V.