Innovative Proteomics Approach to Identify Fluid Biomarkers for Frontotemporal Degeneration
Abstract
The proposed research addresses the FY20 PRMRP Topic Area: Frontotemporal Degeneration and the Area of Encouragement: Research to improve diagnostics of and/or prognostics for frontotemporal degeneration and related proteinopathies. Frontotemporal Degeneration (FTLD) is a group of diseases that is remarkable for the loss of brain cells in the temporal and frontal lobes of the brain. FTLD comprises 10%-20% of all dementias and presents relatively early in life, around the ages of 45-60. It has a negative effect on the quality of life, affecting personality, insight, verbal communication, social behavior, and cognition, with progressive deterioration in all of these characteristics. An additional feature is the progressive language deterioration involving the impairment of speech and the inability to understand words or name objects, and some patients also present with Parkinson-like movement disorders. Upon brain autopsy, different proteins are found in the affected brain areas of patients, with most patients showing accumulations of the Tau or the TDP-43 proteins. One major obstacle in the treatment of FTLD is the difficulty to identify the specific disease protein that is accumulating in a patient’s brain during life. Some clinical presentations have a high likelihood of predicting the underlying pathology but others, including the most common clinical syndrome characterized by behavioral and personality changes, do not. Since it is expected that FTLD patients with Tau and TDP-43 accumulations need distinct treatments, and such treatments are currently being actively pursued, biomarkers that are able to distinguish these two major pathological subtypes are urgently needed. The goal of this project will be to discover new FTLD biomarkers using advanced mass spectrometry analysis of blood plasma and cerebrospinal fluid samples. This project will be enabled through unique and secured access to FTLD patient samples and innovative approaches to identify FTLD-specific proteins. The proposed research will bring the field closer to clinically relevant biomarker signatures for FTLD that separate between FTLD-TDP and FTLD-Tau patients. Upon completion of this project, researchers and clinicians will be able to better stratify patients between types of FTLD in clinical trials. This will allow for tailored results, and the development of specific therapies, based on the specific proteins pathology of the disease. Ultimately, the goal will be to identify the best possible candidate biomarkers for further development into clinical biomarkers that can be used to treat patients with tailored therapeutics.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110712
Entities
People
- Rosa Rademakers
Organizations
- Flanders Institute for Biotechnology
- United States Army