Visual Evoked Potentials as an Early-Stage Biomarker in the rTg4510 Tauopathy Mouse Model

Abstract

Background: Tauopathies such as Alzheimer’s disease (AD) and frontotemporal dementia (FTD) are characterized by formation of neurofibrillary tangles consisting of hyperphosphorylated tau protein. Early pathophysiological and functional changes related to neurofibrillary tangles formation are considered to occur prior to extensive neurodegeneration. Hyperphosphorylated tau has been detected in postmortem retinas of AD and FTD patients, and the visual pathway is an easily accessible system in a clinical setting. Hence, assessment of the visual function may offer the potential to detect consequences of early tau pathology in patients. Objective: The aim of this study was to evaluate visual function in a tauopathy mouse model in relation to tau hyperphosphorylation and neurodegeneration. Methods: In this study we explored the association between the visual system and functional consequences of tau pathology progression using a tauopathy rTg4510 mouse model. To this end, we recorded full-field electroretinography and visual evoked potentials in anesthetized and awake states at different ages. Results: While retinal function remained mostly intact within all the age groups investigated, we detected significant changes in amplitudes of visual evoked potential responses in young rTg4510 mice exhibiting early tau pathology prior to neurodegeneration. These functional alterations in the visual cortex were positively correlated with pathological tau levels. Conclusion: Our findings suggest that visual processing could be useful as a novel electrophysiological biomarker for early stages of tauopathy.