Role of Neural Activity in Alzheimer's Disease

Development of therapeutics for Alzheimer’s disease (AD) has been hampered by a lack of clear understanding of the biology governing its progression. Until recently, the scientific community has been focusing predominantly on the nuanced molecular mechanisms leading to the onset of AD. These approaches have often disregarded perturbations of overall function of the neurons that are vulnerable to Alzheimer’s disease. The research proposed by Dr. Ksenia V. Kastanenka and colleagues is designed to provide significant insight into this area of neural activity and contribute greatly to an unexplored aspect of the disease. The results of this study will build a stronger platform for successful therapeutic agent innovation.

The goal of this project is to explore the importance of neural activity perturbations on the development of AD using an animal model. Dr. Ksenia V. Kastanenka and colleagues are testing whether hyperactivity of neurons in the brain leads to AD pathology. To that end the researchers are expressing a light-sensitive protein in neurons that can be activated with brief flashes of light to induce hyperactivity in these neurons. Subsequently, they measure levels of calcium, which is an important signaling molecule in the brain, and visualizing amyloid plaques. These studies allow neurons to be studied in exquisite detail, using state-of-the-art technology. The team is also testing whether activation of neurons that normally play a role in silencing neural networks in the brain, by light, can restore the balance between excitation and inhibition.
This research will provide great insight into the area of neural hyperactivity that has been greatly unexplored and will build a stronger platform for innovation of successful therapeutic agents.