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The AppNL-G-F mouse retina is a site for preclinical Alzheimer’s disease diagnosis and research
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The AppNL-G-F mouse retina is a site for preclinical Alzheimer’s disease diagnosis and research
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Paper
The AppNL-G-F mouse retina is a site for preclinical Alzheimer’s disease diagnosis and research
2020
Overview
Abstract In this study, we report the results of a comprehensive phenotyping of the retina of the AppNL-G-F mouse. We demonstrate that soluble Aβ accumulation is present in the retina of these mice early in life and progresses to Aβ plaque formation by midlife. This rising Aβ burden coincides with local microglia reactivity, astrogliosis, and abnormalities in retinal vein morphology. Electrophysiological recordings reveal signs of neuronal dysfunction yet no overt neurodegeneration was observed and visual performance outcomes were unaffected in the AppNL-G-F mouse. Furthermore, we show that hyperspectral imaging can be used to quantify retinal Aβ, underscoring its potential as a biomarker for AD diagnosis and monitoring. These findings suggest that the AppNL-G-F retina mimics the early, preclinical stages of AD, and, together with retinal imaging techniques, offers unique opportunities for drug discovery and fundamental research into preclinical AD. Competing Interest Statement The authors declare the following competing interests: XH and PvW have filed an International (PCT) Patent Application No PCT/AU2019/000003 relating to retinal hyperspectral imaging. They are co-founders of Enlighten Imaging PTY LTD, a start-up company focused on developing novel retinal imaging solutions for neurological and retinal diseases. * List of abbreviations AD Alzheimer’s disease Aβ amyloid-beta CNS central nervous system ChAT choline acetyltransferase GFAP glial acidic fibrillary protein GFP green fluorescent protein HSI hyperspectral imaging Iba1 ionized calcium-binding adapter molecule 1 PFA paraformaldehyde RBPMS RNA-binding protein with multiple splicing S100B S100 calcium binding protein B WT wild type
Publisher
Cold Spring Harbor Laboratory Press,Cold Spring Harbor Laboratory
