Catherine Callahan
Pronouns: she/her
Research Mentor(s): Hanna Trzeciakiewicz
Co-Presenter:
Research Mentor School/College/Department: Neurology / Medicine
Presentation Date: April 20
Presentation Type: Poster
Session: Session 5 – 3:40pm – 4:30 pm
Room: League Ballroom
Authors: Catherine Callahan, Annie Li, Henry Paulson, Hanna Trzeciakiewicz
Presenter: 19
Abstract
Alzheimer’s Disease (AD) is the most common form of neurodegeneration accounting for 6.2 million cases in the United States. Dementia presentation in AD patients occurs 10-20 years after the pathological presence and eventual accumulation of amyloid beta plaques and tau protein neurofibrillary tangles (NFTs) within the brain. We focused on the tau protein for the following reasons: 1) The burden of tau protein aggregates most closely correlates with cognitive decline and neurodegeneration and 2) tau and its six protein isoforms, are involved in a multitude of other neurodegenerative diseases. Progressive supranuclear palsy (PSP) is an understudied tau-mediated neurodegenerative disorder clinically diagnosed by ocular motor dysfunction, posture instability, akinesia and cognitive dysfunction and pathologically characterized by an accumulation of globose tangles and tufted astrocytes. It remains a mystery as to how the tau protein is involved in these different neurological disorders like AD and PSP. Post-translational modifications (PTMs), such as phosphorylation that physically alter tau structure and function promote a loss of normal tau function and gain of toxicity. We hypothesized that the PTM profile for tau will be distinct for each tauopathy attributing to the unique accumulations of tau. Using no cognitive impairment (NCI), AD, and PSP human brain tissue (n = 6 per diagnosis) from the Michigan Brain Bank, we extracted the tau protein for mass spectrometry, immunoblotting, and immunohistochemical techniques. Our findings suggest that PSP-tau is hypophosphorylated compared to hyperphosphorylated AD-tau. We further identified preferential tau isoform accumulation in specific brain cells (neurons, astrocytes and microglial). These preliminary findings provide insight into how tau accumulates in different neurological disorders. A furthering of tau PTM profiles could lead to a better understanding of tau pathology within specific neurological diseases like AD and PSP, potentially resulting in targeted approaches for diagnosis and treatment for the tauopathies.
Biomedical Sciences
