Mesoscopic mapping of the visual pathway in a female 5XFAD mouse model of Alzheimer's disease

Abstract Synaptic and network disruption is correlated with cognitive decline and loss of sensation in Alzheimer's disease (AD). Surprisingly, amyloid-β (Aβ) deposition and Aβ-induced neurodegeneration appear in the retina at the early-stage of AD. Although these Aβ-related changes in the retina could cause damage to the visual functions, no studies have yet revealed the alteration in the visual pathway of AD. Therefore, we investigated the alteration of visual circuits in the AD mouse model using anterograde neurotracer. We investigated the Aβ accumulation by immunofluorescent staining in the retina and retinorecipient areas of 4- and 12-month-old female 5XFAD transgenic mice. Following intravitreal injection of cholera toxin β subunits (CTβ) tracer, we evaluated the fluorescence intensity of accumulated CTβ in the retinorecipient areas in 4- and 12-month-old female wild-type and 5XFAD mice. Our results demonstrated that Aβ accumulation 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. Although these results provide the first neuroanatomical evidence for decreased visual connectivity in an AD mouse model, it is difficult to explain cell type-specific connectivity. These findings reveal the Aβ-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.