Investigating Cell-Type Molecular Drivers of Tau Aggregation Using ReN-VM Model
Presenter: Kaushal Kasina
Faculty Sponsor: Jennifer Rauch
School: UMass Amherst
Research Area: Neuroscience and Cognitive Science
Session: Poster Session 1, 10:30 AM - 11:15 AM, 163, C5
ABSTRACT
Protein aggregation and spread is associated with various neurodegenerative conditions and diseases. The accumulation of microtubule-associated protein Tau and its spread are considered to be a hallmark in many forms of dementia such as Alzheimer's disease, frontotemporal dementia, and chronic traumatic encephalopathy. This aggregation occurs when Tau proteins become hyperphosphorylated and, instead of binding to the usual microtubules, binds to other Tau proteins to form insoluble neurofibrillary tangles (NFTs) and ultimately into Tau aggregates. These aggregates have been reported to spread in a predictable manner and the advancement of this spread has been directly linked to neuron degradation and cognitive decline. However, the cause of the spread and its recurring pattern is widely unknown. As Tau aggregates, the different cell types of the CNS (i.e. neurons, astrocytes, oligodendrocytes, and microglia) have a distinct role in the response to Tau and potentially to its spread. To understand how Tau aggregates spread and how it affects the different cell types in the CNS we opted to use an immortalized stem cell derived cell line (known as ReN-VM cells) as our model for our studies. This cell line has the capability of differentiating into Neurons, Astrocytes and Oligodendrocytes. To better understand the role of these cell types in the spread of Tau, we have developed multiple Adeno-Associated Viruses (AAVs). Each AAV has been designed to specifically target different cell types and express fluorescently labeled Tau proteins(i.e. neurons express red, astrocytes green and oligodendrocytes far-red). Using this cell model, we aim to investigate differences in tau aggregation in the unique cell types.
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