Biofluid Core

Mayo Clinic Rochester, Rochester MN

Investigators

Linked publications & trials

Abstract

ABSTRACT – ALLFTD2: BIOFLUID CORE FTLD encompasses a group of fatal neurodegenerative disorders primarily neuropathologically characterized by the aggregation of tau or TDP-43 proteins. No approved treatment for any FTLD syndrome exists owing, in part, to our incomplete understanding of FTLD pathogenesis and to the lack of diagnostic, susceptibility/risk, prognostic, predictive, and response biomarkers. Successfully treating FTLD will require an early and accurate clinical diagnosis, means to discriminate sporadic FTLD participants with tau versus TDP-43 pathology, and the ability to monitor novel intervention effects in clinical trials. Accordingly, the Biofluid Core (BFC) will endeavor to develop novel fluid biomarkers for establishing diagnosis, detecting early-stage disease, monitoring disease progression, and measuring downstream intervention effects. Towards enabling the selection of participants in prevention and early treatment trials, the BFC will also identify biomarkers that predict conversion from asymptomatic mutation carrier status to overt disease. Such fluid biomarkers are particularly important because of their biological specificity, potential low cost and, for blood biomarkers, their accessibility and ease of use in remote and medically underserved communities. Already the BFC has made significant progress towards addressing these priorities during the current ALLFTD cycle, and BFC investigators will build upon their multiple publications and novel datasets generated during the current cycle to expand fluid biomarker discovery. With the current leadership and co-investigators, the BFC is well-poised to continue with FTLD fluid biomarker discovery and development using several novel strategies involving unbiased proteomics, extracellular vesicles, and a de novo protein produced by TDP-43 dysfunction. In addition to refining present biomarkers and developing new tools with improved sensitivity and specificity to support FTLD treatment development, a major role of the BFC is to oversee biospecimen and biomarker data sharing and to help manage collaborative biomarker discovery efforts with academia and industry. With support from the National Centralized Repository for Alzheimer’s Disease and Related Dementias, ALLFTD has been highly successful in sharing biospecimens with academic and industry researchers and is a major international resource for obtaining FTLD biofluid samples. Data generated by the BFC will also be used for hypothesis testing in Project 1 and Project 2. Through these endeavors, the BFC will be well-prepared to directly address the National Alzheimer’s Project Act FTLD research recommendation: to develop new biomarkers to diagnose and support FTLD treatment development.