Paul D. Kassner, Ph.D.
Alzheimer’s disease (AD) is the most common form of dementia and is an incurable, degenerative and terminal disease that is generally diagnosed in people over 65. The original amyloid hypothesis postulated that amyloid beta (Aβ) deposits are the fundamental cause of the disease. Aβ is derived from cleavage of amyloid precursor protein (APP) resulting in various peptide lengths (38-43 amino acids). Although the role of amyloidosis in AD has evolved over the years, aberrant production of Aβ peptides and their aggregation is still believed to play a key pathological role in AD, and has continuously been the focus of AD research.
This seminar will review how an Amgen laboratory identified novel modulators of Aβ Homeostasis via high-throughput siRNA screening. It will review how this lab performed a primary screen on a human CNS-derived cell line amenable to siRNA transfection. It will describe the results of the initial screen and the counter screen performed to filter out genes involved in cell viability. The webinar will conclude by describing the proteins identified with putative novel roles in Aβ processing and the lab’s next steps in further evaluating the function of these proteins via organotypic cultures, RNAi studies, gene knockout studies, and pharmacological tools.