Project Overview

Mitochondria are crucial for the brain as they are the cellular engine providing the energy to this organ. Alterations in mitochondrial activity in dementia have been observed for decades. An established hypothesis suggests that brain mitochondrial dysfunction could cause neurodegenerative diseases and dementia. However, it is unclear whether these alterations are the cause or merely consequences of dementia. Addressing this question will help to understand the causal events in dementia and identify therapeutic targets.

This project aims to determine the role of mitochondria in dementia. In contrast to other organs, the brain is composed of various cell types with different functions. Mitochondria also have distinct roles in these different brain cells. Given that alterations of mitochondria have been observed in different brain cell types, we will examine the role of mitochondria in specific brain cell types.

The hypothesis regarding mitochondria’s causal role in dementia has remained unanswered due to a lack of tools to test a direct link between mitochondria and cognition. We have generated such a tool to increase mitochondrial activity, and its activation in the brain of dementia mouse models improves their memory performance. We will use this tool to increase mitochondrial activity in specific brain cell types and assess its impact on cognitive deficits in mouse models.

A major challenge with dementia is that we still do not perfectly understand how the brain is working. For instance,we are only beginning to recognize the roles of different cell types within the brain. Similarly, the role of mitochondria across these cell types is poorly understood. In this context, identifying the precise mechanisms leading to dementia is difficult. This project will address these gaps and offer promising opportunities for new therapeutic targets.

This project will reveal basic knowledge about the cellular mechanisms underlying dementia. Specifically, we expect to identify the molecular mechanisms and the specific brain cell types involved in dementia. In future projects, we will leverage this knowledge to generate new treatments targeting these mechanisms. Thus, this project will open new lines of research in the field of dementia and, in the long term, have a direct impact on persons with lived experience of dementia.

Principal Investigator

Etienne Hebert-Chatelain , Université de Moncton

Partners and Donors

Alzheimer Society of Canada