Assessing the Effect of Disease-Specific Conformations in the Aggregation and Spread of Microtubule-Associated Protein Tau

Presenter

Alyssa Leigh Stainton

Campus

UMass Amherst

Sponsor

Jennifer Rauch, Department of Biochemistry and Molecular Biology, UMass Amherst

Schedule

Session 5, 3:30 PM - 4:15 PM [Schedule by Time][Poster Grid for Time/Location]

Location

Poster Board A54, Campus Center Auditorium, Row 3 (A41-A60) [Poster Location Map]

Abstract

The aggregation and spread of microtubule-associated protein tau has been implicated as a cause of disease for numerous neurodegenerative diseases, including Alzheimer’s disease (AD), Chronic Traumatic Encephalopathy (CTE), Corticobasal Degeneration (CBD), and Pick’s disease (PiD). However, there is significant heterogeneity in the clinical manifestations and the distribution of tau pathology for each disease. Further, recent advancements in Cryo-Electron Microscopy have provided atomic-level resolution of tau amyloid filaments, revealing distinct structural variation of the ordered fibril core among tauopathies. Thus, it is hypothesized that different conformations of aggregated tau will cause distinct neuropathology because they interact with endogenous tau differently. In this study, tau conformers specific to AD, CTE, CBD, and PiD have been purified and aggregated in vitro. Using fluorescence resonance energy transfer, we have quantified the extent of aggregation for each construct in cell models and assessed the effect of cross-seeding. This approach has the potential to explain the differences in pathology observed across these diseases and contribute to the development of more effective disease-specific treatments.

Keywords

Neurodegenerative Diseases, Tauopathies, Aggregation, Disease-Specific Mechanisms

Research Area

Neuroscience and Cognitive Science

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