Dr. Angelyn Lao

Mathematical modeling of APP processing influenced by SorLA in Alzheimer‘s disease

"I am interested in understanding the interactions among SorLA and the proteins in the APP processing through mathematical modelling."

The processing of Amyloid Precursor Protein (APP), the central pathology of Alzheimer’s disease, undergoes two pathways: amyloidogenic and non-amyloidogenic. The amyloidogenic pathway produces amyloid beta (Aβ) plaque which is a pathological hallmark of Alzheimer’s disease.
The question we focused on is: How does SorLA, the intracellular sorting receptor, influences the processing of APP in Alzheimer’s disease?
It is important to understand how SorLA interacts with the proteins in the processing of APP that eventually reduces the formation of Aβ plaques in Alzheimer’s disease.
We established the mathematical models (without and with compartment details) describing the biochemical networks, including the interactions among SorLA and the proteins in the processing, regulating the decision process between the two pathways. We analyzed the models based on the experimental dose-response data (APP-sAPPα, sAPPβ, Aβ) we produced using the Tet-off mechanism.
The series of dose-response data show a decreasing effect of SorLA to sAPPα and Aβ, and a surprising minimal effect of SorLA to sAPPβ in the APP processing. Our analyses of the mathematical equations suggest that the “compartment model” matches the profile of the experimental dose-response series data for APP-sAPPα and APP-sAPPβ, and the description of the biological knowledge for Aβ in dependence of APP.