A Strategy for Designing a Molecular Probe for Detection of Beta-Amyloid Oligomers

Friday, November 12, 2010: 10:00 AM
255 B Room (Salt Palace Convention Center)
Yang Hu1, Baihao Su1, Chung-sei Kim1, Michael Hernandez1, Jorge Ghiso2 and Jin Ryoun Kim1, (1)Chemical and Biological Engineering, Polytechnic Institute of New York University, Brooklyn, NY, (2)Pathology and Psychiatry, New York University Langone Medical Center, New York, NY

Aggregation of beta-amyloid (Abeta) into a fibrillar structure is known to be implicated in the pathology of Alzheimer's disease. Development of a robust strategy to detect Abeta oligomeric intermediates, previously identified as significant toxic agents, would be highly beneficial in the screening of drug candidates as well as enhancing our understanding of the molecular basis of Abeta oligomerization. Here, we report the development of a novel molecular probe, PG46, displaying the functional linkage between binding to target species and generation of fluorescence signals. PG46 was found to bind to Abeta oligomers and display an increase in fluorescence. No such event was observed when PG46 was co-incubated with Abeta low molecular weight species or Abeta fibrils. The detection occurred within one hour without any additional sample incubation or preparation steps. The functional linkage could be uncoupled by engineering the connection between domains responsible for binding and signaling. We anticipate that the development of a robust strategy for detection of amyloidogenic oligomers described in this study will be directly relevant to a host of other amyloidogenic proteins.

Extended Abstract: File Not Uploaded