New Fluorescent Sensor Array Lights up Alzheimer’s-Related Proteins for Earlier Detection

Many neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, pose a diagnostic challenge in their early stages before symptoms manifest. Identifying disease-related biomarkers like amyloids, which are aggregated proteins, could offer crucial early insights if they can be detected effectively. Now, researchers have developed a new method that employs an array of sensor molecules to illuminate amyloids. This innovation could play a significant role in monitoring disease progression or differentiating various amyloid-related disorders.

In neurodegenerative diseases, a common factor is the disruption of brain communication, often due to “sticky” clumps of misfolded proteins called amyloids that interrupt signal transmission. These amyloids are believed to be integral to Alzheimer’s disease progression, suggesting their potential as early diagnostic markers to broaden treatment possibilities. While radioimaging techniques like positron emission tomography (PET) scans can detect amyloids, they require advanced equipment and generally target only specific amyloids linked to the disease. As an alternative, fluorescence imaging techniques have been investigated for their simpler yet sensitive capability to detect multiple distinct amyloids.

A team of researchers at The University of Sydney (NSW, Australia) set out to develop a fluorescent sensor array specifically for amyloids. This tool aims to monitor Alzheimer’s and other diseases' progression and differentiate atypical amyloids from other naturally occurring amyloid-forming proteins. The team initially combined five coumarin-based molecular probes, each responding with varying fluorescence levels upon encountering amyloids, into an array. They discovered, however, that using just two of these probes, chosen for their strong fluorescence responses, still yielded a highly sensitive detection system and provided a unique fluorescent “fingerprint” for individual amyloids.

The effectiveness of this two-probe array was tested in a simulated biological fluid containing molecules that could potentially disrupt sensing. Nevertheless, the array maintained its high sensitivity and selectivity. Its efficacy was further validated using samples from the brains of mouse models of Alzheimer’s. The researchers noted distinct fluorescence patterns at the early (6 months old) and later (12 months old) stages of the disease. Moreover, the array produced a distinct fluorescence signature for three amyloids typically associated with Alzheimer’s, another disease-related amyloid, and five “functional amyloids” not implicated in the disease. According to the researchers, this tool offers the potential to differentiate between closely related amyloids, paving the way for earlier and more precise diagnosis of amyloid-related diseases.

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