Retinal and cognitive function deficits in the TgF344-AD rat model of Alzheimer’s disease

Abstract

Purpose : Alzheimer’s disease is characterized by accumulation of amyloid-beta plaques and neurofibrillary tangles of Tau protein in the brain, associated with neurodegeneration and deficits in memory and cognition. Retinal pathology has been reported with Alzheimer’s disease as well. Here, we aimed to determine whether the TgF344-AD transgenic rat model of Alzheimer’s disease, which develops progressive brain pathology and cognitive dysfunction similar to patients with Alzheimer’s disease, shows retinal changes associated with cognitive deficits.

Methods : Retinal function was assessed inTgF344-AD transgenic rats (n=7) and wild type littermate controls (Fischer 344 background, n=5) using electroretinography (ERG) at 6 and 15 months of age. Spatial cognition (spontaneous alternation) and exploratory behavior (number of entries) were assessed via Y-maze at 6 and 15 months. Spatial memory was assessed via Barnes maze at 15 months. Rats were euthanized at 16 months, and brains, retinas, and serum were analyzed for amyloid precursor protein (APP) as a marker of disease progression.

Results : TgF344-AD rats exhibited significant cognitive deficits at 15 months of age as measured by Barnes maze (p<0.01), but no changes in spontaneous alternation or exploratory behavior in the Y maze. Significant delays in ERG oscillatory potential (OP) implicit times were observed at 6 months with bright flash (p<0.001) and at 15 months with dim and bright flashes (p<0.01 and p<0.001, respectively). A significant delay was also observed for positive scotopic threshold response (STR) at 15 months (p <0.01). Increased levels of APP were observed in both brains and retinas from TgF344-AD rats.

Conclusions : As expected, cognitive decline was observed in the TgF344-AD transgenic rat model of Alzheimer’s disease. Notably, retinal function may be useful in predicting and diagnosing changes in the brain with Alzheimer’s disease, as we observed deficits in ERG components generated by the inner retina (OPs) and retinal ganglion cells (STR), suggesting these retinal cell types are vulnerable to Alzheimer’s pathology. This work provides a basis for pursuing non-invasive retinal analysis, including ERG, as a way to stage Alzheimer’s disease.

This is a 2021 ARVO Annual Meeting abstract.