Plaque-associated microglial polarization in visual brain regions of the 5xFAD mouse model.

Introduction: Alzheimer's disease (AD), a neurodegenerative disorder associated with amyloid beta (Aβ) plaque deposition, leads to cognitive decline in affected individuals. Vision changes are among the reported symptoms in AD with studies showing both decline in functions performed by the visual system as well as associations between vision loss and cognitive impairment in AD patients. Due to the increasing number of individuals diagnosed with AD and its early impact on vision, we sought to provide an in-depth analysis of how Aβ, a primary pathology typically preceding many other AD-associated pathologies, affects visual regions of the brain and how microglia, key immune regulators of the brain's environment, respond to this AD-like pathology. Methods: Amyloid pathology was examined in histological sections containing the dorsolateral geniculate nucleus (dLGN), and the primary visual cortex (V1), suprachiasmatic nucleus (SCN), and superior colliculus (SC) of 5xFAD mice using thioflavin-S and anti-amyloid staining. Microglia morphology was analyzed in Iba1 antibody-stained sections and phagocytic activity was evaluated with CD68 co-staining. Results: We found that in the pathway for image-forming vision, including the dLGN and V1, there was significant Aβ pathology, shifts in microglial morphology to an amoeboid state, localization of microglia around plaques, and increased Iba1/CD68 co-labeling. However, in non-image-forming visual brain regions such as the SC and SCN, there was minimal Aβ pathology, ramified microglial morphology, and minimal phagocytic activity. Conclusion: Overall, Aβ plaque deposition was related to brain-region-specific differences in microglial responses, indicating that visual brain regions are differentially affected by AD pathology in the 5xFAD mouse model of amyloidosis.