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 an early detection of these oligomers. Current techniques, such as fluorescence correlation spectroscopy (FCS), are valuable for studying Aβ aggregation but are unsuitable for routine use in clinical settings. This study investigates the potential of Aβ autofluorescence as a diagnostic tool using steady-state fluorescence spectroscopy, a more accessible and practical technique. Aβ40 exhibits autofluorescence dominated by tyrosine emission, which undergoes a spectral shift and quenching during oligomerization. Additionally, a distinct aggregation-induced emission in the visible spectral region correlates with Aβ oligomer concentration, 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 behaviors were observed, including reversible and kinetically trapped aggregate populations. This intrinsic fluorescence approach eliminates the need for extrinsic probes, simplifying experimental procedures and reducing artefacts. The findings suggest that autofluorescence could serve as a straightforward, sensitive, and accessible method for detecting early oligomers, with potential applications in early AD diagnostics.