Biomarkers: Next generation CNS and biofluid markers (Milestone 9.B)
In Progress
Timeline Start - End
2014 - 2024Research Implementation Area
BiomarkersAccelerate the development of the next generation CNS imaging ligands and biofluid molecular signatures targeting a variety of disease processes (neuroinflammation, bioenergetic/metabolic compromise, oxidative stress, synaptic pathology) that can be used as research tools or developed into diagnostic, prognostic, theragnostic or target engagement biomarkers.
Success Criteria
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Initiate synthesis and testing of CNS imaging ligands (PET/SPECT) for at least 12 novel, prioritized candidate targets. Ensure that these reagents are made available as open source tools for target validation and predictive drug development.
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Identify at least 6 multi-omic biomarker signatures (metabolomic, proteomic, cell-free RNAseq etc.) that can be quantitatively measured in peripheral fluids and have been validated across at least 3 diverse cohorts.
Summary of Key Accomplishments
NIA-supported researchers have developed five new PET ligands for five different, novel targets related to synaptic function, oxidative stress and neuroinflammation. These new ligands are being evaluated in animal models and in human brain samples. In addition, one of the main goals of the NIA-supported Molecular Mechanisms of the Vascular Etiology of AD (M2OVE-AD) Consortium is to discover molecular biomarker signatures that can be measured in blood samples that reflect disease processes in the brain.
The key accomplishments summary is current as of March 2022.
Accomplishments/Implementation Activities
Funding Initiatives
- PAR-15-359: Novel Approaches to Diagnosing Alzheimer's Disease & Predicting Progression (R01)
- RFA-AG-15-010: Interdisciplinary Research to Understand the Vascular Contributions to Alzheimer's Disease (R01)
- PAR-16-266: Development and Application of PET and SPECT Imaging Ligands as Biomarkers for Drug Discovery and for Pathophysiological Studies of CNS Disorders (R01)
- PAR-18-596: Research on Current Topics in Alzheimer's Disease and Its Related Dementias (R01)
- NOT-AG-18-001 (#3): in vivo Synaptic Function in Alzheimer's Disease and Related Dementias
- RFA-AG-17-054: Enhancing the Target and Biomarker Discovery Efforts of the AMP AD and M2OVE-AD Consortia (R01)
- PAR-20-037: Development and Application of PET and SPECT Imaging Ligands as Biomarkers for Drug Discovery and for Pathophysiological Studies of CNS Disorders (R01 Clinical Trial Not Allowed)
- PAR-20-037: Development and Application of PET and SPECT Imaging Ligands as Biomarkers for Drug Discovery and for Pathophysiological Studies of CNS Disorders (R01 Clinical Trial Not Allowed)
- PAR-20-038: Development and Application of PET and SPECT Imaging Ligands as Biomarkers for Drug Discovery and for Pathophysiological Studies of CNS Disorders (R01 Clinical Trial Optional)
- NOT-AG-22-032: Development of Radiotracers for Diagnosis and Clinical Studies in Alzheimer's Disease (AD) and AD-Related Dementias (ADRD)
Research Programs and Resources
- Molecular Mechanisms of the Vascular Etiology of Alzheimer's Disease (M²OVE-AD) Consortium
- Quantification of Neuroinflammation in Alzheimer's Disease Using Diffusion Basis Spectrum Imaging
- Imaging Oxidative Stress in an Animal Model of AD with PET
- Neuro-PET Radiotracer Discovery for Imaging Glycogen Synthase Kinase-3
- Longitudinal Molecular Imaging of Neuropathology and Serotonin in Mild Cognitive Impairment
- Select projects funded in FY21
- [18F]-PU-AD epichaperome PET imaging probe
- Sigma-1 Receptor Radioligand for Translational Research in Alzheimer's Disease