Alzheimer's Progression Deciphered

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Mathematical models uncover the complexities of Alzheimer’s disease progression.
Posted On: May 14, 2024
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(L-R) Dr. Giulio Bonifazi, who recently received his PhD in Dr. Maurizio De Pittà’s lab; Dr. Maurizio De Pittà, a Scientist at the Krembil Research Institute.

Researchers from UHN’s Krembil Brain Institute have delved into the intricate relationship between neuron hyperactivity and the accumulation of amyloid-β protein, unveiling promising pathways for early diagnosis and intervention of Alzheimer’s disease. 

Alzheimer’s is a slow-progressing disease that can start years before any noticeable symptoms appear. Without any known cure, early detection and treatment of the disease is critical. One key player identified in the progression of Alzheimer’s is amyloid-β (Aβ), a protein that accumulates in the brain and triggers excessive neuronal activity, which has been associated with the development of the disease.   

A team led by Dr. Maurizio De Pittà, Krembil Brain Institute Scientist and senior author of the study, applied mathematical models to explore the relationship between Aβ and excessive neuronal activity. 

“In this study, we used mathematical models to mimic the intricate processes underlying Alzheimer’s,” explains Dr. De Pittà. “These models enable us to simulate, analyze, and predict the interaction between Aβ and neuronal activity over time.” 

Researchers found a complex relationship between Aβ and neuronal activity.  A build-up of Aβ initiates a cascade of events that leads to excessive neuronal activity. This heightened activity, in turn, can also increase Aβ production, establishing a cycle that drives disease progression.  

The researchers highlighted that the relationship between Aβ accumulation and neuronal hyperactivity differs from one brain region to another. Thus, understanding variations in brain activity across different regions can provide valuable insights into the diverse and intricate manifestations of Alzheimer’s disease.  

“By unravelling the complex interactions in the brain, we can identify new avenues for early detection and targeted treatment,” concludes Dr. Giulio Bonifazi, a previous PhD student in Dr. De Pittà’s lab and first author of the study. “With further research and clinical trials, these findings hold promise for transforming the diagnosis and management of Alzheimer’s disease.” 

This work was supported by “la Caixa” foundation, the Krembil Foundation, BIOEF – Basque Foundation for Health Innovation and Research, the Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED) and UHN Foundation. Dr. Maurizio De Pittà is an Assistant Professor in the Department of Physiology at the University of Toronto. 

Bonifazi G, Luchena C, Gaminde-Blasco A, Ortiz-Sanz C, Capetillo-Zarate E, Matute C, Alberdi E, De Pittà M. A nonlinear meccano for Alzheimer's emergence by amyloid β-mediated glutamatergic hyperactivity. Neurobiol Dis. 2024 May. doi: 10.1016/j.nbd.2024.106473.


Hyperactive brain cells have been associated with Alzheimer’s disease and can disrupt communication between brain cells, ultimately contributing to cognitive decline and other symptoms of the disease.