Alzheimer's disease is marked by the buildup of amyloid plaques in the brain, but most ways of studying these deposits in mouse models require sacrificing the animals. That limits researchers' ability to follow how the disease develops or how treatments work over time. A new study, published in Neurophotonics , describes a fiber-optic method that can monitor plaque signals in living, freely moving mice, opening the door to more flexible testing of potential therapies.
The team, led by researchers at the University of Strathclyde and the Italian Institute of Technology, adapted fiber photometry—a technique commonly used to record neural activity—to detect amyloid plaques. Instead of relying on genetically encoded sensors, they used Methoxy-X04, a fluorescent dye that crosses the blood-brain barrier and binds specifically to amyloid fibrils.
In initial experiments, the researchers used flat optical fibers in anesthetized Alzheimer's model mice (known as 5xFAD mice) and found that the fluorescence signals correlated strongly with plaque density measured afterward in brain slices. A machine learning model was able to distinguish between plaque-bearing and healthy animals based on these depth profiles alone.
Next, the team tested tapered optical fibers, which capture signals from different depths in the brain. In brain tissue slices, the tapered fibers reliably tracked plaque distribution. When implanted chronically in living mice, the fibers revealed depth-specific increases in fluorescence after Methoxy-X04 injection—but only in Alzheimer's model mice, not in healthy controls. Importantly, the technique worked in awake, freely moving animals and showed age-dependent increases in signal consistent with disease progression.
Compared with existing methods such as two-photon microscopy or optoacoustic tomography, the new fiber-based approach allows long-term monitoring of deep brain regions without anesthesia. The researchers note that while the technique cannot resolve individual plaques, it provides a minimally invasive way to track pathological changes across time and brain regions.
The authors suggest that this method could help scientists test how potential treatments affect plaque buildup in real time, accelerating the development of new Alzheimer's therapies.
For details, see the original Gold Open Access article by N. Byron et al., " Depth-resolved fiber photometry of amyloid plaque signals in freely behaving Alzheimer's disease mice ," Neurophotonics 12(3), 035014 (2025), doi: 10.1117/1.NPh.12.3.035014 .
