Investigating the Contribution of Astrocytic-Dependent Inflammation on Amyloid-Induced Tau Pathology

Brain inflammation regulated by microglia and astrocytes is emerging as a contributor to Alzheimer’s disease. While recent studies suggest that microglia certainly play a role in the development of the disease, the role of astrocytes has not been extensively evaluated despite being the most abundant glial cell type in the brain. Our studies show that the upregulation of an ion pump in astrocytes induces astrogliosis and progresses tauopathy, a pathological feature in Alzheimer’s disease. These studies highlight that inflamed astrocytes potentially contribute to Alzheimer’s disease progression. Perhaps suppressing their reactivity may be beneficial in reducing brain inflammation and delaying dementia in Alzheimer’s disease.

2020

An emerging pathophysiological mechanism influencing Alzheimer’s disease (AD) is neuroinflammation, characterized by elevated levels of pro-inflammatory molecules, reactive astrocytes and microglia that span across the course of the disease, potentially influencing disease progression. The role of astrocytes and their contribution to AD development and progression has remained mostly unexplored. In the proposed studies, we aim to determine the influence of astrocytic-dependent inflammation on progressing tau pathology in the presence of plaque burden. Additionally, we aim to identify a mechanism by which astrocytes expressing apolipoprotein E4 display neurotoxicity. These studies will clarify the therapeutic potential of reactive astrocytes and potentially provide new therapeutic targets.