Innovative Fiber-Optic Technique Enables Real-Time Tracking of Alzheimer's Plaques in Freely Moving Mice

Researchers have developed a groundbreaking fiber-optic method that allows scientists to monitor amyloid-beta plaques in the brains of live, freely moving mice, opening new avenues for Alzheimer's disease research. Traditional techniques often require sacrificing animals to study plaque formation, limiting insights into disease progression and treatment efficacy over time.

The new approach adapts fiber photometry, a technique traditionally used to record neural activity, to detect amyloid plaques non-invasively. Instead of genetically encoded sensors, the method employs Methoxy-X04, a fluorescent dye capable of crossing the blood-brain barrier and binding specifically to amyloid fibrils. This dye enables real-time visualization of plaque accumulation.

Initial experiments utilized flat optical fibers in anesthetized Alzheimer's model mice (known as 5xFAD mice). The fluorescence signals obtained correlated strongly with plaque density measured in brain slices afterward. Using machine learning models, the team could distinguish between mice with plaques and healthy controls based solely on depth-profile fluorescence data.

Subsequently, the researchers used tapered optical fibers, which are capable of capturing signals from different depths within the brain tissue. These fibers reliably tracked plaque distribution in brain slices and, when implanted chronically, revealed depth-specific increases in fluorescence after Methoxy-X04 injection. Importantly, the technique was effective in awake, freely moving mice and showed increases in signals with age, consistent with disease progression.

Compared to existing imaging tools like two-photon microscopy or optoacoustic tomography, this fiber-based method provides a minimally invasive way to monitor deep brain regions over extended periods without anesthesia. While it cannot resolve individual plaques, it offers a valuable tool for tracking the overall progression of amyloid pathology in vivo.

The potential applications include testing the effects of therapeutic interventions in real-time, thereby accelerating the development of Alzheimer's treatments. This innovative approach signifies a significant step toward more flexible and comprehensive in vivo studies of neurodegenerative disease mechanisms.

Source: https://medicalxpress.com/news/2025-09-fiber-optic-method-real-alzheimer.html