Mesoscopic Mapping of Visual Pathway in a Female 5XFAD Mouse Model of Alzheimer’s Disease

Abstract

Amyloid-β (Aβ) deposition and Aβ-induced neurodegeneration appear in the retina and retinorecipient areas in the early stages of Alzheimer's disease (AD). Although these Aβ-related changes in the retina cause damage to the visual functions, no studies have yet revealed the alterations in the visual pathways of AD. Therefore, we investigated the alterations of visual circuits in the AD mouse model using anterograde tracer cholera toxin β subunits (CTβ). Moreover, we investigated the Aβ accumulation in the retina and retinorecipient areas and the neuronal loss, and synaptic degeneration in retinorecipient areas by immunofluorescent staining of 4- and 12-month-old female 5XFAD transgenic mice. Our results demonstrated that Aβ accumulation and neurodegeneration occurred in the retina and retinorecipient regions of early and late stages of the 5XFAD mice. Retinal efferents to the suprachiasmatic nucleus and lateral geniculate nucleus were impaired in the early stage of AD. Moreover, retinal connections to the dorsal lateral geniculate nucleus and superior colliculus were degenerated in the late-stage of AD. These findings reveal the Aβ-related pathology induced visual circuit disturbances at the mesoscale level in both the early and late stages of AD and provide anatomical and functional insights into the visual circuitry of AD.