Validation of a biomarker that could identify a subset of Frontotemporal Dementia and Alzheimer's disease patients

Project Summary

The overall goal of this project is to find a biomarker that will identify a subset of people with Alzheimer’s disease (AD) and Frontotemporal Dementia (FTD) that have a pathological accumulation of TAR DNA-binding protein (TDP-43) in their brains. To date, attempts to directly measure pathological TDP-43 in patient samples have been unsuccessful. Therefore, we propose to measure the production of truncated stathmin 2 (STMN2), as a surrogate marker for TDP-43. Truncated STMN2 is produced as a result of the inability of TDP-43 to function properly due to its incorporation into pathological aggregates. First, we will determine if the production of truncated STMN2 in the brain is specific to AD and FTD patients with TDP-43 aggregation and not healthy individuals. We will also investigate the prognostic value of truncated STMN2 by evaluating if elevated levels are correlated with age of disease onset and disease progression. Our next aim is to develop the tools needed to detect truncated STMN2 at both the RNA and protein level in blood and cerebrospinal fluid. We anticipate that the levels of truncated STMN2 will be able to discriminate patients with TDP-43 aggregation from healthy individuals and patients with other types of pathology. Our overall goal is to validate truncated STMN2 as a biomarker for AD and FTD with TDP-43 pathology and develop diagnostic tools for its detection in patients. With these methods in place we can identify which patients would be most likely to benefit from emerging therapies.