Assessing retinal thickness and vascular structures in an Alzheimer's disease mouse model APP NL‐F/NL‐F

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Aims/Purpose: In Alzheimer's disease (AD), there are histopathological aspects that cannot be studied in patients, demanding the use of murine models of the disease. The APPNL‐F/NL‐F model reproduces the pathophysiology quite faithfully. The aim of the present study was to analyze the retinal vascular structures and retinal thickness in an AD model at different ages and compares these findings to age‐matched wild type (WT) controls.Methods: A diachronic study was conducted using spectral‐domain OCT angiography (SD‐OCTA) and AngioTool software to assess retinal vascular structures, alongside OCT for measuring inner and outer retina thickness. We include two study groups: the APPNL‐F/NL‐F AD model and WT controls at 6, 9, 12, 15, 17, and 20 months old. The analysis focused on the three vascular plexus and retinal thickness, using the Early Treatment Diabetic Retinopathy Study (ETDRS) sectors. We considered statistically significant a p‐value < 0.05.Results: Compared to WT, the APPNL‐F/NL‐F group exhibited both vascular and structural changes starting as early as 6 months, with these changes persisting and evolving at 15, 17, and 20 months. Significant vascular alterations, particularly in the superficial vascular complex (SVC), were noted. There was a marked decrease in vessel area and total vessel length in the SVC, as well as in the intermediate and deep capillary plexus. Additionally, the inner retina predominantly showed a thickness decrease, while the outer retina demonstrated an increased thickness at most time points compared to the control group.Conclusions: The study identifies early retinal vascular and structural changes in the APPNL‐F/NL‐F model that precede cognitive changes observed at later stages. These findings suggest that the retinal changes in this model more closely resemble those in human AD compared to other transgenic models, highlighting the potential of retinal assessments in early AD diagnosis.