Creation of AD-Relevant Isogenic Lines with the Gene Editing Method CasMasTREE
Brycelyn Whitman, Arizona State University, Undergraduate Student
Since 1901, Alzheimer's disease (AD) claims at least 5.5 million individuals each year, making it the sixth leading cause of death in the United States. Alzheimer's disease is an age-related neurodegenerative disorder denoted by severe memory deterioration due to amyloid beta and tau. These proteins are known for creating knots and tangles within the brain, ultimately causing neuronal death and memory loss. AD has two forms: familial AD (FAD) and sporadic AD (SAD). About 70% of the population is affected by SAD, meaning that AD can develop because of the interplay of many genes. Currently, there is no known cure or treatment for patients suffering with FAD and SAD. However, research has found that some genes, such as Apolipoprotein E (APOE) isoforms 2, 3, and 4, play a role in genetic risk of developing SAD. Specifically, the isoform, APOE 4, has been linked to the increased risk of developing AD, while the isoform, APOE 2, has been linked to decreased risk of developing AD. How these genes increase the risk of AD is not well understood, but every gene found linked to Alzheimers can increase the understanding of the disease forms. Since the majority of AD cases are sporadic, it makes this disease difficult to study in vitro. Thus, there is a need for the ability to create isogenic lines to study single genes and their roles in neurodegenerative diseases.