Imaging Amyloid and Tau in the Retina: Current Research and Future Directions

The retina is a key focus in the search for biomarkers of Alzheimer's disease (AD) because of its accessibility and shared development with the brain. The pathological hallmarks of AD, amyloid beta (Aβ), and hyperphosphorylated tau (pTau) have been identified in the retina, although histopathologic findings have been mixed. Several imaging-based approaches have been developed to detect retinal AD pathology in vivo. Here, we review the research related to imaging AD-related pathology in the retina and implications for future biomarker research.

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Curcumin fluorescence and hyperspectral imaging are both promising methods for detecting retinal Aβ, although both require validation in larger cohorts. Challenges remain in distinguishing curcumin-labeled Aβ from background fluorescence and standardization of dosing and quantification methods. Hyperspectral imaging is limited by confounding signals from other retinal features and variability in reflectance spectra between individuals. To date, evidence of tau aggregation in the retina is limited to histopathologic studies. New avenues of research are on the horizon, including near-infrared fluorescence imaging, novel Aβ labeling techniques, and small molecule retinal tau tracers. Artificial intelligence (AI) approaches, including machine learning models and deep learning-based image analysis, are active areas of investigation.

Although the histopathological evidence seems promising, methods for imaging retinal Aβ require further validation, and in vivo imaging of retinal tau remains elusive. AI approaches may hold the greatest promise for the discovery of a characteristic retinal imaging profile of AD. Elucidating the role of Aβ and pTau in the retina will provide key insights into the complex processes involved in aging and in neurodegenerative disease.