Alzheimer’s Disease (AD) is characterized by dysregulation of neurons involved in memory, which is believed to be caused by the production of an agent termed “amyloid beta”. Amyloid beta spreads across the brain during the progression of Alzheimer’s disease, with the current belief being that hyperactive neurons drive this spread in the brain. However, to date identifying these hyperactive neurons has remained elusive.

Our laboratory has recently discovered a new type of neuron that embodies key features of AD: these neurons are involved in cognition, are hyperactive, are found within a brain region that is very susceptible to AD, and form direct connections to other AD-vulnerable brain regions. We will study this new type of neuron to evaluate its role in causing amyloid beta spread, and test new drugs targeting this neuron to slow AD progression.

Our research uses a combination of mouse work to study AD in behaviour, along with circuit, cellular, and molecular mechanisms. We will study AD using state-of-the-art experimental methodologies and machine learning analysis to reveal AD-associated changes and determine new drug targets and treatments. Our combination of model system and tools make our research wholly unique worldwide.

In our preliminary studies studying a hyperactive neuron type, we have identified a drug target within these cells that has FDA-approved drugs in other clinical settings, which we will repurpose for intervention in AD. We will directly test this drug, and others emerging from our study, in interventional experiments. Success in our research will lead to new approaches to help prevent the progression of AD.

Revealing the types of neurons that drive AD progression may be invaluable for identifying new drug targets and treatments. Our work has revealed type of neuron that seems to be critical for driving AD. We will we study this neuron with state-of-the-art technology to understand how it changes in AD, and disrupt dysregulation of this neuron with new drugs to prevent AD progression. Our work here has the potential to ultimately help discover new treatments for AD.