Designing Probes to Detect Amyloid Plaques in Patients with Alzheimer’s Disease

Undergraduate #157
Discipline: Chemistry and Chemical Sciences
Subcategory: Biomedical Engineering

Nathalie Bravo Batista - North Carolina Central University
Co-Author(s): Nathan Wymer

Alzheimer’s disease (AD) develops every 66 seconds in someone in the Unites States. Development of an effective cure against this disease is one of the world’s top public health priorities. Amyloid plaques are one of the two brain abnormalities that define AD. Plaques form when protein pieces called beta-amyloid clump together. However, the Blood Brain Barrier (BBB) prevents the entrance of most molecules, including chemical probes, such as antibodies, to our brain, limiting our understanding of most of the functions of our brain and delaying the development of effective cures to brain related diseases and disorders. Our laboratory is engineering to probes that can get through the BBB and can bind to the amyloid plaques, and detect amyloid plaques earlier in the progression of the disease. A major component of the probe is the carrier protein CRM197. CRM197 is a non-toxic mutant of diphtheria toxin, currently used as a carrier protein for polysaccharides and haptens to make them immunogenic. This carrier protein is thought to play an important role in the active transport of molecules across the BBB. The human and mouse homolog of CRM197 receptors have been expressed in E. coli. Next, we will generate a chimeric molecule using CRM197 and the mouse homolog of the receptor. Use of the this probe will be for early detection, which can help slow the development of Alzheimer’s disease and impact the design of future treatment options for Alzheimer’s disease patients.

Funder Acknowledgement(s): Nathan Wymer

Faculty Advisor: Nathan Wymer, nwymer@nccu.edu

Role: Last summer, the goal for the experiment was to isolate the CRM197 carrier protein; this summer, our goal was to make the mouse and the human protein express with the Pet19. I was involved with almost everything in the experiment, I had to do literature research, and I also worked with the process of making E. coli express the human and mouse versions of CRM197 receptors.