Targeting the Adaptive Immunity to Prevent Alzheimer's Brain Degeneration

To reduce or prevent the infiltration of T-cells into the brain, a critical detrimental event driving Alzheimer’s brain degeneration.

Neurodegenerative diseases such as Alzheimer’s disease involve the buildup of tau proteins and significant brain degeneration. This tau-mediated damage is mainly driven by inflammation in the brain, with recent evidence of infiltrating T-lymphocytes (T-cells) being essential to this process. This project will apply multidisciplinary approaches to determine the candidate signaling pathway(s) responsible for attracting T-cells to the brain in disease, and to block T-cell infiltration to prevent subsequent tau-mediated brain degeneration in a genetically modified mouse model.

This project will take advantage of a multidisciplinary approach derived from unique expertise to answer our hypothesis. This work will determine novel signaling pathways and mechanism(s) by which peripheral T-lymphocytes infiltrate the brain using newly generated genetically modified mice and multiple models of disease. By targeting adaptive immunity in the context of Alzheimer’s dementia, this project may lead to a direction for developing novel effective therapies.

By blocking or preventing the infiltration of these immune cells into the brain, the completion of this project further advances the field in two ways. First, it enhances our understanding of the signaling pathways mediating the complex interactions between adaptive immunity and the brain. Second, it utilizes experimental therapeutic approaches to provide a proof of concept for the drug discovery process. By providing a novel direction for therapeutics, this potentially opens up new opportunities to provide effective treatments to those with Alzheimer’s dementia.