Apolipoprotein ε2 Potential Protection Against Long Term Consequence of Traumatic Brain Injury: Thesis Proposal

Traumatic brain injury (TBI) is one of the highest causes of death in the United States to date, while also posing long-term neurological effects. Research has shown that the APOE ε2 gene is a protective gene against some neurodegenerative diseases such as Parkinson's and Alzheimer’s (Shinohara, M., 2020). This study will investigate the potential neuroprotective effects of Apolipoprotein ε2 (APOE2) as a genetic approach to a possible resilience to TBI, using Drosophila melanogaster as a model organism. Utilizing transgenic flies, expressing APOE ε2 with another fly with the UAS-CNS line, allows for a progeny line with APOE ε2 in their central nervous system using the Gal4-UAS system. We hypothesize the inclusion of the APOE ε2 gene will reduce the short and long-term effects, providing a potential resilience to TBI. The HIT protocol will be used, this mechanical impact model will inflict blunt force, stimulating traumatic brain injury. In a controlled laboratory setting the flies will be subjected to a TBI event. Observations through behavioral testing, ectopic protein detection and measuring mortality rate. We predict that APOE ε2 carriers may have a resilience effect against TBI involving pathways associated with lipid metabolism and inflammation. This research will enhance our understanding of how genetic factors can influence resilience to TBI and lead to new therapeutic strategies and recovery, especially for those who are susceptible to multiple blunt force trauma to the head such as, law enforcement, military service people, and those who participate in contact sports.