The AppNL-G-F mouse retina is a site for preclinical Alzheimer's disease diagnosis and research

Acta Neuropathol Commun. 2021 Jan 6;9(1):6. doi: 10.1186/s40478-020-01102-5.

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 revealed 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.

Keywords: Alzheimer’s disease; Electroretinogram; Hyperspectral imaging; Mouse model; Retina; Retinal imaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Protein Precursor / genetics
  • Animals
  • Disease Progression
  • Electroretinography
  • Gliosis / metabolism
  • Gliosis / pathology
  • Hyperspectral Imaging
  • Mice
  • Mice, Transgenic
  • Microglia / pathology
  • Microglia / physiology
  • Peptide Fragments / metabolism
  • Phenotype
  • Plaque, Amyloid / metabolism*
  • Plaque, Amyloid / pathology
  • Plaque, Amyloid / physiopathology
  • Retina / metabolism*
  • Retina / pathology
  • Retina / physiopathology
  • Retinal Neurons / physiology
  • Retinal Vein / pathology
  • Tomography, Optical Coherence

Substances

  • APP protein, human
  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Peptide Fragments
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)