Abstract
Objective: To determine if tau pathology contributes to deficits in vision by conducting behavioral tests and histology to assess visual acuity in an Alzheimer’s disease (AD) mouse model.
Background: Understanding the timing and progression of Alzheimer’s pathology in the visual system can help inform interventions that may slow neurodegeneration. Research shows that visual deficits and accumulation of retinal amyloid beta and phosphorylated tau (ptau) pathologies may precede onset of cognitive decline in Alzheimer’s disease (AD).
Design/Methods: Viewing the relationship between AD pathology and vision, we examined two transgenic AD mouse models (Htau and 3xtg) and their respective controls (tau null and C57BLK6J) for visual deficits and pathological changes to brain regions that receive visual information. We assessed these variables across ages representing pre-pathological, emerging pathology, and progressing pathology disease states. Visual behavior tests were conducted using a fully-automated system to measure optomotor response in order to provide estimates of visual acuity.
Results: At pre-pathological ages, 3xtg mice had lower visual acuity than controls. With increasing age, both htau and 3xtg had reduced visual acuity compared to controls. There were no statistical differences between males and females of any strain in visual acuity at the ages tested; therefore, data are averaged across both sexes for each strain. To assess brain pathology, immunofluorescent histological labeling techniques were used to identify amyloid beta, ptau, and inflammation in retinorecipient brain structures. Both htau and 3xTg mice show increased presence of Aβ, ptau and microglia inflammation in the SC at a prepathological age of 3 months compared to C57 and tau null mice.
Conclusions: Retinal AD pathology precedes development of pathology in brain areas responsible for cognition—making visual disturbances and detection of retinal pathology potential early biomarkers for AD. Future work will view AD pathology in these strains (and other AD models) throughout the central visual pathway in the brain.
Disclosure: Dr. Mistry has nothing to disclose.
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