ArticleJournal of biomedical optics2026
Longitudinal three-photon imaging for tracking amyloid plaques and vascular degeneration in a mouse model of Alzheimer's disease.
Article in Journal of biomedical optics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Significance: Vascular abnormalities may contribute to amyloid-beta accumulation and neurotoxicity in Alzheimer's disease (AD). Monitoring vascular degeneration as AD progresses is essential. Three-photon fluorescence microscopy enables high-resolution deep tissue imaging with minimal invasiveness and photodamage. Aim: In this proof-of-concept study, we established a longitudinal 3P imaging pipeline to quantify vascular and amyloid plaque changes in the Approach: A cranial window allowed repeated 3P imaging at 4-week intervals beginning at 5 weeks after surgery. Vessels labeled with Texas-Red were segmented using DeepVess, whereas plaques labeled with methoxy-XO4 were segmented using custom scripts. Quantitative analyses assessed vascular parameters (diameter, tortuosity, length, inter-vessel distance, total volume) and plaque metrics (radius, total volume). Results: We imaged the same field over 4 weeks, quantifying an overall decrease in vasculature and an increase in amyloid plaques between two sessions. Significant changes in vessel diameter, inter-vessel distance, and alterations in vessel length and plaque radius were observed. Changes in vessel tortuosity were not significant. Conclusions: We demonstrate the potential of three-photon imaging to track vascular and amyloid-related changes in deep cortical structures. It offers a tool for studying the interplay between vascular and amyloid pathologies in AD, supporting future research into disease mechanisms and therapeutic strategies.
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