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Title: | Characterizing Apolipoprotein E as a Therapeutic Target for Traumatic Brain Injuries |
Authors: | Nooka, Avani |
Advisors: | Notterman, Daniel |
Department: | Molecular Biology |
Certificate Program: | Global Health and Health Policy Program |
Class Year: | 2024 |
Abstract: | Repetitive traumatic brain injuries (TBIs) are a global health concern associated with high rates of morbidity, mortality, and economic impact. While the distinct binding affinities of Apolipoprotein E (APOE) isoforms are well-studied therapeutic targets in Alzheimer's disease, their roles in lipid transport and neuroprotection in rTBIs remain unexplored despite sharing similar pathophysiological mechanisms. This study examines the differential impacts of APOE isoforms, specifically APOE2 and APOE4, on rTBI outcomes using Drosophila melanogaster as a model organism. I analyzed longevity, locomotor, and decision-making outcomes following injuries in transgenic flies that express the human APOE isoforms. I also developed a light-dark chamber apparatus to assess changes in learning and short-term memory performance. Our findings reveal that APOE2 enhances longevity and learning post-rTBI, suggesting a protective role against mortality and cognitive impairments. Conversely, APOE4 is associated with reduced lifespan and increased learning deficits, consistent with its link to accelerated neurodegeneration. Notably, the observed increase in locomotion in male flies expressing APOE4 may indicate a human behavioral phenomenon of aggression post-injury, more frequently observed in males than females with an equivalent head injury, which supports further testing. Additionally, the initial recovery in decision-making performance from 1 to 7 Days post-injury in wild-type flies indicates potential cognitive recovery trajectories following TBIs. Overall, this study underscores the neuroprotective potential of APOE2 and the detrimental effects of APOE4, highlighting the importance of isoform-specific pathways in TBI pathophysiology and introducing a novel apparatus for testing short-term memory. The potential protective properties of APOE2 bridge a significant gap in TBI therapy and warrant further investigation of the emphasized complexity in developing tailored treatments based on individual genetic profiles. |
URI: | http://arks.princeton.edu/ark:/88435/dsp01pk02cf07j |
Type of Material: | Princeton University Senior Theses |
Language: | en |
Appears in Collections: | Molecular Biology, 1954-2024 Global Health and Health Policy Program, 2017-2023 |
Files in This Item:
File | Description | Size | Format | |
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NOOKA-AVANI-THESIS.pdf | 2.78 MB | Adobe PDF | Request a copy |
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