Characterization of the retinal changes of the 3×Tg-AD mouse model of Alzheimer’s disease

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder whose diagnosis remains a notable challenge. The literature suggests that cerebral changes precede AD symptoms by over two decades, implying a significantly advanced stage of AD by the time it is usually diagnosed. In the study herein, texture analysis was applied to computed optical coherence tomography ocular fundus images to identify differences between a group of the transgenic mouse model of the Alzheimer's disease (3×Tg-AD) and a group of wild-type mice, at the ages of one and two-months-old. A substantial difference between groups was found at both time-points across all neuroretina's layers. Here, the inner nuclear layer stands out both in the level of statistically significant differences and on the extension of these differences which span through the imaged area. Also, the progression of AD is suggested to be spotted by texture analysis as demonstrated by the significant difference found in the inner plexiform and the outer nuclear layers from the age of one to the age of two-months-old. These findings demonstrate the potential of the use of the retina and texture analysis to the diagnosis of AD and monitor AD progression. Besides, the differences between groups found in this study suggest that the 3×Tg-AD model may be inappropriate to study early changes associated with the AD and other animal models should be tested following the same path and rationale. Moreover, these results also suggest that the human genes present in these transgenic mice may have an impact on the neurodevelopment of offspring which would justify the significant changes found at the age of one-month-old.

Normative mice retinal thickness: 16-month longitudinal characterization of wild-type mice and changes in a model of Alzheimer's disease

“…Based on OCT imaging, retinal changes induced by neurodegenerative diseases have been found, including changes in retinal layer thickness (Cunha et al, 2016 ; Song et al, 2020 ; Salobrar-García et al, 2021 ). Recently, we have also shown that retinal texture biomarkers can help discriminate between age-matched healthy controls and animal models of Alzheimer's disease (AD) in the early stages (Nunes et al, 2019 ; Ferreira et al, 2020 , 2022 ; Guimarães et al, 2022 ).…”

Retinal imaging in animal models: Searching for biomarkers of neurodegeneration

“…This results in a total of 80 features (20 features × 4 quadrants) per layer (5) per acquisition time point (7), which were then subjected to feature selection (described in Statistical Analysis). Further details on the feature extraction process can be found in (21).…”