Senior Honors Thesis: "Modeling the Spread of Amyloid in Patients with Alzheimer's Disease"

Abstract:  Alzheimer’s disease (AD) is a progressive neurodegenerative disease that leads to cognitive and functional impairment. Patients with AD often suffer from severe memory loss and problems with language and emotion. One possible cause of the disease is the accumulation of pathogenic amyloid plaques in the brain. Researchers have developed Pittsburg compound B (PiB) to image amyloid plaques in neuronal tissues. In this project, we collaborate with the Neurology department at Washington University School of Medicine, and try to model the spread of amyloid with respect to PiB readings along functionally connected paths in patients with AD. We are able to get the connectivity matrix of the brain and the PiB data of 138 patients at two time points roughly three years apart from the School of Medicine. The proposed model suggests that the amount of amyloid at a particular brain site depends on local growth following a sigmoid function and diffusion from related sites based on the connectivity matrix. The goal is to find the diffusion coefficient and the autocatalysis coefficient that provide the best predictive value. By using a MATLAB function called lsqcurvefit, we are able to get the best fitting coefficients for each patient. However, the model only works for patients who have a big change in the total amount of amyloid between two readings. For those who have a small change between readings, the model does not have much predictive value. More biological insights are necessary to account for the results and to improve the model.

Advisor: John McCarthy