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Plaque-associated microglial polarization in visual brain regions of the 5xFAD mouse model
Shaylah McCool1,2, Arnav Jain1, Jennie C Smith1
1Department of Ophthalmology and Visual Sciences, Truhlsen Eye Institute, University of Nebraska Medical Center, Omaha, NE, United States.
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.
Insights
Alzheimer's disease amyloid beta plaques impact image-forming visual brain regions more than non-image-forming regions. Microglia respond to amyloid pathology in image-forming areas, indicating region-specific effects in the 5xFAD mouse model.
Area of Science:
- Neuroscience
- Immunology
- Ophthalmology
Background:
- Alzheimer's disease (AD) is linked to amyloid beta (Aβ) plaques and cognitive decline.
- Vision changes are common in AD, with links between vision loss and cognitive impairment.
- Aβ pathology precedes other AD pathologies and impacts the visual system early.
Purpose of the Study:
- To analyze how Aβ affects visual brain regions.
- To investigate microglial responses to Aβ in the visual system.
- To understand region-specific AD pathology in the visual pathways.
Main Methods:
- Examined Aβ pathology in visual regions (dLGN, V1, SCN, SC) of 5xFAD mice.
- Used thioflavin-S and anti-amyloid staining for Aβ.
- Analyzed microglia morphology (Iba1) and phagocytic activity (CD68).
Main Results:
- Significant Aβ pathology and amoeboid microglia with increased phagocytosis in image-forming regions (dLGN, V1).
- Minimal Aβ pathology and ramified microglia with low phagocytosis in non-image-forming regions (SC, SCN).
- Aβ plaque deposition correlated with region-specific microglial responses.
Conclusions:
- Aβ deposition differentially affects visual brain regions in the 5xFAD mouse model.
- Microglial responses vary based on Aβ presence in visual pathways.
- This highlights the specific impact of AD pathology on visual processing areas.
