ORCID ID
Graduation Date
Spring 5-9-2026
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Programs
Interdisciplinary Graduate Program in Biomedical Sciences
First Advisor
Matthew J. Van Hook
Abstract
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the formation of amyloid beta (Aβ) plaques and neurofibrillary tangles (NFTs) coupled with clinical manifestations such as behavioral, motor, and cognitive impairments. Sensory changes in AD are frequently documented with vision changes being among the earliest reported symptoms. Due to the increasing prevalence of AD and its early impact on vision, the goal of this research was to determine whether Aβ plaques disrupt neuronal and synaptic structure and function in the visual system, the immune response to these plaques, and whether additional AD-like pathology such as tau is required for visual dysfunction in AD. In the 5xFAD mouse model of amyloidosis, photoreceptor dysfunction was seen in the absence of structural changes. In the dorsolateral geniculate nucleus (dLGN), the thalamic relay for conscious vision, a decreased density of retinal ganglion cell (RGC) axon terminals and fewer thalamocortical (TC) neurons were seen with no detectable deficits in excitatory synaptic function, TC neuron dendritic structure, or abnormalities in reflexive visual behavior. In the pathway for image-forming vision – the dLGN and primary visual cortex (V1), there was significant Aβ pathology, shifts in microglial morphology to an amoeboid state, and increased phagocytic activity. However, in non-image-forming visual brain regions such as the superior colliculus (SC) and suprachiasmatic nucleus (SCN), there was minimal Aβ pathology, ramified microglial morphology, and minimal phagocytic activity. In the 3xTg-AD mouse model, which presents with amyloid and tau pathology, neither is detected in the dLGN wherein RGC axon terminals and synaptic function are maintained. However, microgliosis was observed in the dLGN as evidenced by an increase in cell count and altered morphology. Taken together, these results indicate that even with histopathological evidence of disease in the brain and concurrent microglial polarization in these severely impacted regions, there were few detectable effects on visual system structure and function which may be an attempt to preserve function in the face of Aβ pathology and that other pathological features of AD may play a larger role in visual system dysfunction in AD.
Rights
The author holds the copyright to this work and any reuse or permissions must be obtained from the author directly.
Recommended Citation
McCool, Shaylah, "Effects of Amyloid Beta on Visual System Structure and Function" (2026). Theses & Dissertations. 1065.
https://digitalcommons.unmc.edu/etd/1065