Exploiting Click-Chemistry and Microfluidics to Map the Neuronal Itinerary of APP Processing and Amyloid-Beta Generation

Namratha Srinivas, Washington University in St. Louis

Permanent URL: https://doi.org/10.7936/K7057CVC


Alzheimer’s disease (AD) is a chronic neurodegenerative disease and is the sixth leading cause of death in the United States with approximately 5.5 million Americans diagnosed with it. The neuropathological hallmark includes extracellular senile plaques and intraneuronal neurofibrillary tangles. Recent GWAS studies have identified genes associated with AD, and have revealed several classes of genes implicated in disease pathogenesis. In particular, three general pathways associated with an increased risk of AD included: 1) cholesterol metabolism, innate immune system, and the membrane trafficking. Our lab has focused on intracellular trafficking as it relates to the processing of amyloid precursor protein (APP), the precursor protein for the Aβ peptide—a critical component of the senile plaque. Much is still unknown about the intracellular itinerary of APP, and the cellular location of Aβ production. Here, I describe the use of click-chemistry applied to an APP construct to further study APP processing. In addition, I describe work that I did to develop a microfluidic system to enable visualizing APP processing within the unique cytoarchitecture of primary neurons. Microfluidics helps in isolating the soma and axon to understand APP processing in these specific compartments.