Abstract
Purpose :
Neurodegeneration in Alzheimer Disease (AD) is caused by aggregation of amyloid-β plaques and formation of tau neurofibrillary tangles (NFT). While NFTs are a hallmark of AD, the misfolding and oligomerization of tau protein can start up to 15 years before the first symptoms of dementia. Detecting the disease at an early stage can be complicated and costly. Evidence shows that the visual system follows the pathology in the brain. Indeed, studies have shown significant changes in the visual evoked potentials (VEPs) in patients with mild cognitive impairment as well as AD. The aim of our study was to evaluate whether changes in visual processing may represent an early biomarker of pathological Tau accumulation.
Methods :
An animal model of tauopathy, Tg4510, exhibits progressive accumulation of pathological Tau species and neurodegeneration. Transgenic mice at ages of 6, 9 and 16 months were studied against their age matched controls. Retinal response to a white light stimulus was recorded using electroretinography (ERG). Electroencephalography was simultaneously performed to record VEPs. The stimulus was applied at eight different intensities with an appropriate interval in between flashes.
Results :
While ERG responses at 6, 9 and 16 months did not differ between transgenic (tg) and control animals, an age-dependent decline in retinal response was observed regardless of genotype. On the other hand, VEP responses to a light stimulus were significantly more pronounced in 6 month tg animals compared to age matched control mice. At 9 months, the difference between tg and control animals was slightly diminished. By 16 months of age, the VEPs in tg mice were weaker compared to their age matched controls, possibly reflecting extensive neuronal loss.
Conclusions :
Our findings in younger animals (6 months) may indicate that compensatory mechanisms precede extensive neuronal loss and Tau accumulation. Further histological analysis will help establish the level of correlation between tauopathy and visual processing, which would further strengthen its value as a biomarker
This is a 2021 ARVO Annual Meeting abstract.