Depth-resolved fiber photometry of amyloid plaque signals in freely behaving Alzheimer's disease mice
Byron, N.; McAlinden, N.; Pisano, F.; Pisanello, M.; Ferreira, J.; Montinaro, C.; Mathieson, K.; De Vittorio, M.; Pisanello, F.; Sakata, S.
Show abstract
Alzheimers disease pathology typically manifests itself across multiple brain regions yet assessment at this scale in mouse models remains a challenge. This hinders the development of novel therapeutic approaches. Here we introduce a novel fiber photometry approach to monitor amyloid pathology in freely behaving mice. We first demonstrated that flat fiber-based photometry can detect amyloid signals across multiple brain regions under anesthesia after injecting a blood-brain barrier permeable tracer, Methoxy-X04. The depth profile of in vivo fluorescent signals was correlated with postmortem histological plaque signals. After confirming its feasibility ex vivo, we chronically implanted a tapered fiber for depth-resolved fiber photometry in freely behaving mice. After injecting Methoxy-X04, fluorescent signals increased in a depth-specific manner in Alzheimers mice, but not in wild-type littermates. While fiber photometry has been widely adopted to monitor neuronal and non-neuronal activity, our approach expands the capabilities to monitor molecular pathologies such as amyloid plaques, even in a freely behaving condition.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.