Abstract

.Significance: As one part of the central nervous system, the retina manifests neurovascular defects in Alzheimer’s disease (AD). Quantitative imaging of retinal neurovascular abnormalities may promise a new method for early diagnosis and treatment assessment of AD. Previous imaging studies of transgenic AD mouse models have been limited to the central part of the retina. Given that the pathological hallmarks of AD frequently appear in different peripheral quadrants, a comprehensive regional investigation is needed for a better understanding of the retinal degeneration associated with AD-like pathology.Aim: We aim to demonstrate concurrent optical coherence tomography (OCT) and OCT angiography (OCTA) of retinal neuronal and vascular abnormalities in the 5XFAD mouse model and to investigate region-specific retinal degeneration.Approach: A custom-built OCT system was used for retinal imaging. Retinal thickness, vessel width, and vessel density were quantitatively measured. The artery and vein (AV) were classified for differential AV analysis, and trilaminar vascular plexuses were segmented for depth-resolved density measurement.Results: It was observed that inner and outer retinal thicknesses were explicitly reduced in the dorsal and temporal quadrants, respectively, in 5XFAD mice. A significant arterial narrowing in 5XFAD mice was also observed. Moreover, overall capillary density consistently showed a decreasing trend in 5XFAD mice, but regional specificity was not identified.Conclusions: Quadrant- and layer-specific neurovascular degeneration was observed in 5XFAD mice. Concurrent OCT and OCTA promise a noninvasive method for quantitative monitoring of AD progression and treatment assessment.

Highlights

  • Alzheimer’s disease (AD) is a progressive neurodegenerative disease and the fifth leading cause of death in Americans over 65 years.[1]

  • Quadrant- and layer-specific neurovascular degeneration was observed in 5XFAD mice

  • Concurrent optical coherence tomography (OCT) and OCT angiography (OCTA) promise a noninvasive method for quantitative monitoring of AD progression and treatment assessment

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Summary

Introduction

Alzheimer’s disease (AD) is a progressive neurodegenerative disease and the fifth leading cause of death in Americans over 65 years.[1]. Beta-amyloid (Aβ) deposits in the retina were found to be associated with brain Aβ burden,[9,10] and morphological and functional impairments of the retina were observed in AD patients.[11,12] Given the clear optics of the eye, the retina offers easy accessibility to ocular imaging modalities, enabling noninvasive, cost-effective, and rapid screening to define at-risk AD populations. Over the past decade, substantial progress has been made in retinal imaging techniques, such as retinal fluorescent imaging,[13] fluorescence lifetime imaging,[14] hyperspectral imaging,[15] spectrophotometric fundus imaging,[16] optical coherence tomography (OCT),[17] and OCT angiography (OCTA),[18] to detect AD-associated abnormalities

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