Abstract 2426 Say “ADU” to Alzheimer's: The Role of Aducanumab in Treating Alzheimer's Disease

Alzheimer's disease (AD) is a chronic brain disorder that slowly destroys a person's memory and thinking skills. Researchers have identified neurofibrillary tangles (NFTs) of the hyperphosphorylated tau protein (p-tau) in patients who have tauopathies, diseases characterized by tau inclusion in the brain, such as Alzheimer's disease. Another hallmark of Alzheimer's Disease is Amyloid Beta protein (Aβ) plaques, which accumulate when Aβ proteins cluster in the neuron synapses after they bind with APOE4. While the relationship between these two variables is unclear, the neurological implications and degenerative effects have been clearly established: hyperphosphorylated tau cannot effectively stabilize neurons, and Aβ plaques cause inflammation, trigger toxic mechanisms, and lead to vascular dysfunctions, all of these consequently are responsible for neuron death. However, a newly Food and Drug Administration-approved antibody, Aducanumab, has the potential to treat Alzheimer's disease by decreasing p-tau and the formation of Aβ plaques. This effectively mitigates the progression of neuronal deterioration and Alzheimer's Disease. Aducanumab binds to Aβ on the negatively charged Glu3 and Asp7 residues of Aβ. Aβ monomers cluster into oligomers and fibrils, increasing the surface area of the aggregates and consequently giving Aducanumab a greater affinity to bind to the Aβ clusters and successfully remove the Aβ in the process of microglial-mediated clearance. By understanding the process of Aβ clearance, researchers can more effectively work to develop functional treatments for Alzheimer's Disease. The Mahtomedi Center for BioMolecular Modeling SMART Team used 3-D modeling and printing technology to examine structure-function relationships of APOE4 and Aβ in AD patients. This visual model will be a valuable tool in developing our story.