Year of Publication

2023

College

Arts and Sciences

Department/School/Program

Neuroscience

Degree Name

Bachelors of Science

Faculty Advisor

Adam Bachstetter

Abstract

Although neurodegenerative diseases are often clinically distinct, they typically share common pathological markers. One of the most common causes of clinical dementia is Alzheimer’s disease (AD). Pathologically, AD is defined by the presence of intercellular tangles composed of hyperphosphorylated tau proteins and extracellular plaques made of abnormally cleaved amyloid-beta proteins. However recent genome-wide association studies have also found that many of the predispositions for AD are located on or near genes highly expressed in microglia. In the healthy CNS, microglia act as the brain’s immune system and are chiefly involved in neuronal support and maintaining homeostasis throughout the CNS. Typically, microglia are in a quiescent state surveying their local microenvironment. However, in the presence of injury or disease, microglia are tasked with the clearance of foreign pathogens to return the CNS to homeostasis. While there is no clear link between disease and changes in microglia phenotype, recent studies speculate that increased microglial activity exacerbates neurodegenerative disease progression, particularly in the early stages. To understand changes that occur following disease or injury, animal models are widely used to recapitulate human disease and their biomarkers. A new model of AD-associated pathology known as AppSAAmice possess 3 genetic variations associated with AD and show increased expression of amyloid protein deposits. Using our recently published method of multiplex staining and analysis (QUIVER), we stained and characterized changes in microglia, particularly in the presence of AD-associated pathology. Using high-volume multiplexed staining allows for populations of microglia to be identified in relation to disease pathology and other cell types in the aging and injured brain. Understanding the changes occurring at the single-cell level in microglia and their spatial association with disease pathology may allow for better insight into the role of microglia in disease.

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