Project description
Novel high-throughput biomarker tools for neurodegenerative diseases
Finding therapies for Alzheimer’s disease (AD) and other neurodegenerative dementias (NDDs) requires the development of specific biomarker assays. The ERC-funded FLUBIODEM project aims to develop high-throughput biomarker tools for the analysis of large cohort studies. The combination of biomarker data with clinical, imaging, and genetic information will provide comprehensive molecular disease phenotypes to enable disease stratification, drug discovery, and translational research. The central project goal is to discover new biomarkers for NDD pathologies, including non-AD tau pathology. The study will employ general and targeted cerebrospinal fluid proteomics and novel cell type-biased tandem mass tag proteomics to identify biomarkers specific for neuronal, astrocytic, and microglial cells, and their activation states.
Objective
Critical to our understanding of Alzheimer’s disease (AD) and other neurodegenerative dementias (NDDs), as well as to finding disease-modifying therapies, is the development of biomarkers for the underlying disease processes. To facilitate improved diagnostics and drug discovery, we have developed methods to measure markers of amyloid and tau pathology, central and peripheral nervous system injury, astrocytic and microglial activation, as well as neuroinflammation. Our most exciting advancement in this field so far is the development of phosphorylated tau assays sensitive enough to measure this protein in plasma to detect AD pathology in the brain and to allow for disease stratification and monitoring based on AD pathology. I now propose to develop new high-throughput biomarker tools that will enable the analysis of large cohort studies combining clinical, imaging, genetic and biomarker data to provide truly comprehensive molecular disease phenotypes that will inform interventions, drug discovery and translational research, clinical trial stratification, detection of risk and resilience factors (lifestyle-related, as well as genetic), and ultimately drive the quest towards clinically accessible personalised medicine in the NDD field. A large part of the research efforts will be focused on discovering new biomarkers for TDP-43 and α-synuclein pathologies, non-AD tau pathology, and lysosomal and synaptic dysfunction, through general and targeted proteomics on CSF samples, and through employing a novel cell type-biased tandem mass tag proteomics workflow to discover biomarkers related to neuronal, astrocytic, and microglial cells, and their different activation states. Promising CSF biomarkers will be examined in blood; biomarker candidates that are measurable in this matrix and correlate with CSF will be developed into sensitive and specific blood tests using cutting-edge technology, as we have previously done for Aβ40, Aβ42, T-tau, P-tau, NfL, and GFAp.
Fields of science
- medical and health sciencesbasic medicinepharmacology and pharmacydrug discovery
- medical and health sciencesbasic medicineneurologydementiaalzheimer
- medical and health sciencesbasic medicinepathology
- medical and health scienceshealth sciencespersonalized medicine
- engineering and technologymedical engineeringmedical laboratory technologylaboratory samples analysis
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Topic(s)
Funding Scheme
HORIZON-AG - HORIZON Action Grant Budget-BasedHost institution
405 30 Goeteborg
Sweden