Retinal analysis of a mouse model of Alzheimer’s disease with multicontrast optical coherence tomography

Abstract

Recent Alzheimer's disease (AD) patient studies have focused on retinal analysis, as the retina is the only part of the central nervous system which can be imaged non-invasively by optical methods. However as this is a relatively new approach, the occurrence and role of pathological features such as retinal layer thinning, extracellular amyloid beta (Aβ) accumulation and vascular changes is still debated. Animal models of AD are therefore often used in attempts to understand the disease. In this work, both eyes of 24 APP/PS1 transgenic mice (age: 45-104 weeks) and 15 age-matched wildtype littermates were imaged by a custom-built multi-contrast optical coherence tomography (OCT) system. The system provided a combination of standard reflectivity data, polarization-sensitive data and OCT angiograms. This tri-fold contrast provided qualitative and quantitative information on retinal layer thickness and structure, presence of hyper-reflective foci, phase retardation abnormalities and retinal vasculature. While abnormal structural properties and phase retardation signals were observed in the retinas, the observations were very similar in transgenic and control mice. At the end of the experiment, retinas and brains were harvested from a subset of the mice (14 transgenic, 7 age-matched control) in order to compare the in vivo results to histological analysis, and to quantify the cortical Aβ plaque load. arXiv:1909.08466v2 [physics.med-ph]

TheAppNL-G-Fmouse retina is a site for preclinical Alzheimer’s disease diagnosis and research

“…With one exception 40 , this phenotype is thus far unstudied in AD mouse models and our data suggest that the App NL-G-F retina can be used to further explore this retinal manifestation of AD. Notably, an explanation for the diverging and more severe phenotype of many other transgenic AD mouse models may be sought in the fact that those models are far removed from the human disease state, with nonendogenous promotors, overexpression of APP byproducts, PS1 mutation and/or abnormal APP and Aβ expression levels.…”

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

“…The need for the early detection of changes unfolding in the CNS due to Alzheimer's disease is of utmost, and increasing, importance as life expectancy is steadily increasing [1] and the prevalence in people aged 65 and older reached the two figures in 2019 in the USA [2]. Furthermore, it is hypothesised that AD has advanced over two decades when detected by state-of-the-art means [4,5], hampering the access to the first pathophysiological changes caused by AD and tracking their progress. While the use of the retina as a window into the CNS has been used, mostly resorting to thickness measurements, these studies should be taken into account carefully as the generally claimed thinning of the retina is not exclusive to AD.…”

“…Diagnosis of Alzheimer's disease (AD) remains a major challenge. Simple diagnostic to identify early biomarkers for tracking the onset and progression of AD would be of retina and the brain have the same embryonic origin [5], which makes the retina the only part of the central nervous system (CNS) directly accessible through non-invasive optical means. This hypothesis allows performing non-invasive studies, in vivo and in situ, at any time along the lifespan of the person or animal being studied.…”

Scattering Angle Resolved Optical Coherence Tomography Detects Early Changes in 3xTg Alzheimer's Disease Mouse Model

“…In a similar cross-sectional pilot study, Harper et al 73 used multi-contrast OCT (standard reflectivity data, PS data, and OCT angiograms) to examine the retinas of a transgenic AD mouse model. Their study compared 24 APP/PS1 transgenic mice (age, 45-104 weeks) and 15 age-matched controls.…”

“…Other similar studies have also been unable to segment out the NFL in mice. 73 Still, quantifiable patterns are present in superficial layers. Furthermore, each mouse volume was manually inspected in five B-scan locations to ensure the accuracy of the segmentation algorithm.…”