Intrinsic Visible Emission of Amyloid-β Oligomers: A Potential Tool for Early Alzheimer’s Diagnosis

Alzheimer’s disease (AD) is a major public health challenge in ageing societies, with its onset occurring years before symptoms appear. In recent decades, growing evidence has identified soluble amyloid-β (Aβ) oligomers as key species in the pathogenesis and diagnosis of AD, underscoring the urgent need for early detection methods. Fluorescence spectroscopy techniques using extrinsic fluorescent labels, such as fluorescence correlation spectroscopy (FCS), are valuable for studying Aβ aggregation in vitro but are unsuitable for routine use in clinical settings due to their complexity and limited applicability in biological fluids. This study investigates the intrinsic fluorescence of Amyloid-β(1–40), Aβ40, as a label-free approach to detecting and characterising the oligomers formed during the early stages of aggregation. Aβ40 exhibits autofluorescence dominated by tyrosine emission, which undergoes strong blue shift and quenching during oligomerization. Additionally, an aggregation-induced emission 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 of Aβ40 (cac1 = 0.5 µM and cac2 = 19 µM), distinct aggregation behaviours are observed, which are in agreement with the results of previous aggregation studies. By employing steady-state fluorescence spectroscopy, a widely accessible and practical technique, these findings establish a direct link between Aβ early aggregation and intrinsic-fluorescence changes, demonstrating their potential as a tool for detecting and analysing Aβ oligomers. This approach eliminates the need for extrinsic probes, simplifying experimental procedures and reducing artefacts, making it a promising strategy in the context of early AD diagnostics.