Defining the unique immunogenetic landscape of PSP compared to related dementias

Pathway Grant

Principal Investigator: Dr. Jessica Rexach, UCLA

In our study, we aim to decipher the genetic underpinnings of Progressive Supranuclear Palsy (PSP) related to immune function. We will use sequencing data from over 10,000 individuals (including 3,748 PSP patient samples) to run genomics analyses that are focused on a specific region of DNA called the HLA locus, which plays a crucial role in our immune system. This region is known to be highly variable among individuals. Our goal is to compare the genetic makeup of the HLA locus in people affected by PSP compared to those with Alzheimer’s disease (AD) and the general population. We want to find out which genetic factors are common to both diseases and which are unique to each. In simple terms, we’re looking for clues in the DNA that could explain how changes in the immune system might influence why some individuals develop these conditions. We’re particularly interested in how the immune system is involved in these diseases because of its therapeutic potential. Imagine it as a puzzle – we’re searching for the pieces that connect receptors and ligands, which are like messengers controlling our immune responses. These messengers can vary in people with PSP and AD. By understanding these variations, we hope to gain insights into what goes wrong in the brain tissue of individuals with these conditions that can be leveraged for immune-based therapies.