Intrinsic visible emission of amyloid-β oligomers: a potential tool for early alzheimer's diagnosis

Abstract

Alzheimer's disease (AD) is a major public health challenge, with its onset occurring years before symptoms appear. Soluble amyloid-β (Aβ) oligomers are key species in AD pathogenesis and diagnosis, highlighting the need for early detection. This study investigates the intrinsic fluorescence of Aβ(1–40) (Aβ40) as a label-free approach to detecting early-stage oligomers. Aβ40 exhibits autofluorescence dominated by tyrosine emission, which undergoes a strong blue shift and quenching during oligomerization. Additionally, aggregation-induced emission (AIE) in the visible spectral region emerges, correlating with Aβ oligomer concentration and providing a means to detect and quantify oligomers. At the critical aggregation concentrations cac₁ = 0.5 μM and cac₂ = 19 μM, distinct aggregation behaviours are observed. By employing steady-state fluorescence spectroscopy, a widely accessible technique, these findings establish a direct link between early Aβ aggregation and intrinsic fluorescence changes. This approach eliminates the need for extrinsic probes, simplifying experimental procedures and reducing artefacts. Although further studies are required to develop a robust quantitative correlation for potential diagnostic applications, Aβ autofluorescence represents a promising strategy for investigating early aggregation processes in the context of AD.