TY - JOUR

T1 - Visual Evoked Potentials as an Early-Stage Biomarker in the rTg4510 Tauopathy Mouse Model

AU - Parka, Aleksandra

AU - Volbracht, Christiane

AU - Hall, Benjamin

AU - Bastlund, Jesper F.

AU - Nedergaard, Maiken

AU - Laursen, Bettina

AU - Botta, Paolo

AU - Sotty, Florence

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - Alzheimer’s disease

KW - electroretinography

KW - frontotemporal dementia

KW - rTg4510

KW - tauopathies

KW - visual evoked potentials

U2 - 10.3233/JAD-220964

DO - 10.3233/JAD-220964

M3 - Journal article

C2 - 37005884

AN - SCOPUS:85159554122

VL - 93

SP - 247

EP - 262

JO - Journal of Alzheimer's Disease

JF - Journal of Alzheimer's Disease

SN - 1387-2877

IS - 1

ER -