The retina as a window to early dysfunctions of Alzheimer's disease following studies with a 5xFAD mouse model.

Alzheimer's disease (AD) is a progressive neurodegenerative disease leading to neuronal dysfunctions with cognitive impairment. AD can affect visual pathways and visual cortex and result in various visual changes and problems. However, how early the visual dysfunctions occur in AD is still a matter of discussion. Here, we used electrophysiological techniques to show the presence of early anomalies in AD visual system. To this aim, we used a familial AD (FAD) model, the 5xFAD transgenic mouse, characterized by severe progressive amyloid pathology and cognitive deficits. We investigated the retina and primary visual cortex responsivity together with behavioral assessment of the visual acuity. Visual tests and recordings were conducted at different ages in 5xFAD mice, corresponding to different phases of neurodegeneration and beta amyloid accumulation. We showed that the visual system is impaired in 5xFAD mice. In particular, we found that the inner retina impairment precedes neuronal disorders in other brain areas and cognitive deficits. Thus, noninvasive retinal electrophysiology can provide a support for assessing early visual dysfunctions in AD.