Hyperspectral retinal imaging in mouse models of proteinopathies identifies disease‐specific signatures

Purpose Previous research in the AppNL‐G‐F mouse has shown that hyperspectral retinal imaging (HSRI) can be used to quantify retinal amyloid burden in the preclinical stages of Alzheimer’s disease (AD) [1]. This underscores its potential as an imaging biomarker for AD diagnosis and monitoring. One prerequisite for the rational implementation of HSRI as a biomarker, however, is a better understanding of the pathological correlate of the HSRI signature. In this follow‐up study, we explored HSRI signatures in different proteinopathies and identified the pathological features underlying the observed HSRI results. Methods Retinal tissues were collected from mouse models with amyloid, tau and alpha‐synuclein overexpression/aggregation for ex vivo HSRI (Snapscan, Imec) [1]. HSRI was complemented with optical coherence tomography and electroretinograms (prior to HSRI) and immunohistochemistry and molecular studies of protein aggregation (after HSRI). Results While all protein aggregates led to HSRI changes in the 450–600 nm range, distinct signatures were observed for amyloid, tau and alpha‐synuclein. Furthermore, the observed HSRI changes correlated with levels of the protein oligomerization and aggregation. Diverging patterns of retinal dysfunction/degeneration were observed in the different mouse models, illustrating the varied impacts of these protein aggregates on retinal structure and function. Conclusions HSRI may be used to quantify retinal amyloid, tau and alpha‐synuclein, underscoring its potential as a biomarker for diagnosis and disease monitoring. Moreover, our data suggest that amyloid, tau and alpha‐synuclein accumulation lead to distinct HSRI signatures, thus adding further evidence that HSRI may have utility in the diagnosis and stratification of proteinopathies associated with the most common forms of neurodegenerative diseases. Bibliograph Vandenabeele et al. (2021) Acta Neuropathol Commun 9(1):6.