Adaeze Okafor
The Role of APP Intracellular Domain in Alzheimer’s Disease

SchoolOrange High School

ProgramScience

MentorSanjay Pimplikar, PhD, and Kaushik Ghosal, PhD

DepartmentNeurosciences

Hypothesis: It is widely believed that amyloid precursor protein intracellular domain fragment (AICD) plays an unappreciated role in Alzheimer’s disease (AD). Specifically, there is speculation that AICD contributes to AD by enhancing both neuroinflammation and the hyper-phosphorylation of tau proteins. We seek to determine the role that AICD plays in Alzheimer's disease, specifically the effects it has on neuroinflammation and the hyperphosphorylation of tau proteins.

Methodology: Transgenic (Tg) mice were generated to express AICD in the hippocampal regions of the brain. Some were given an anti-inflammatory drug that may reduce the risk of AD. Wild type (WT) mice served as the control group. Hemi brains were treated, then mounted onto slides with glycerol. Microscopy was performed using a Leica DMR microscope.

Outcomes: We found that AICD transgenic mice display pathological features found in AD. The AICD transgenic mice showed an increase in phosphorylation of tau and the presence of neuroinflammation. In addition, the utilization of NSAIDs as an anti-inflammatory drug proved successful. These neurodegenerative changes have been detected in both human and mice brains with AD. These findings are important because they suggest that in addition to AD, AICD causes pathological features of AD.

Interpretations

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