Understanding the Role of a Suppressed Immune System in Frontotemporal Dementia

The goal of this project is to understand if immune cell exhaustion is implicated in FTD and if it can be therapeutically targeted to alleviate symptoms.

I previously published findings that showed immune cells outside of the brain, which carry FTD-associated mutations, have a dampened immune response. A dampened immune response is often associated with immune cell exhaustion (ICE), when immune cells lose the ability to respond to infections and inflammation. Here we will investigate 1. The downstream effects of ICE on other immune cells, and 2. How ICE in the periphery contributes to degeneration and inflammation in the brain. The completion of this proposal will inform us of the role of ICE in FTD and whether this is a potential therapeutic target.

The completion of this proposal will inform us of the role of immune cell exhaustion in FTD and if this is a potential therapeutic target. This is a highly novel approach given that inflammation has been viewed as rampant in neurodegenerative disease and should be dampened in order to be therapeutically beneficial. If our hypothesis is correct, and the immune system is indeed exhausted in FTD, alternative therapeutic approaches will need to be sought.

The completion of this proposal will provide rationale for testing alternative immunotherapies that aim to rejuvenate the immune system in FTD as well as other dementias, as opposed to traditional therapies aimed at suppressing inflammation. This challenges the prevailing dogma that neuroinflammation in PD is purely detrimental and should be broadly dampened.