Novel Tracers and Emerging Targets for Positron Emission Tomography in Alzheimer's Disease and Related Dementias

Day 1 (Wednesday, March 12)

9:15 a.m. Opening Remarks

Session 1 | Integrated Platforms
Highly integrated platforms are operational to allow the collection, harmonization, dissemination and sharing of protocols and PET data, in combination with clinical phenotype and multimodal biomarkers, from multiple sites. Large scale studies have enabled the definition of thresholds and facilitate the systematic assessment of risk and disease modifiers.

9:30 a.m. Harmonization of PET data for the analyses of multiple cohorts: Overview of SCAN and ADNI. Bill Jagust, University of California, Berkeley

10:00 a.m. Clinical use of PET in the "real world": Overview of the IDEAS/new IDEAS studies. Gil Rabinovici, University of California, San Francisco

10:30 a.m. Longitudinal multicenter head-to-head harmonization of tau PET tracers: The HEAD Study. Tharick Pascoal, University of Pittsburgh, and Suzanne Baker, University of California, Berkeley

11:00 a.m. Impact of co-pathologies and introduction of CLARiTI. Sterling Johnson, University of Wisconsin and C. Dirk Keene, University of Washington

Session 2 | Modeling Disease Spread and Progression
Besides assisting diagnosis, the ability of PET to provide quantitative information with high specificity, at regional level, in vivo, along the lifespan, remains uniquely attractive to illuminating the pathophysiology of AD and used in concomitance with additional approaches, allows to elaborate models of disease spread and progression.

11:30 a.m. Temporal models of disease progression and PET-based "clocks". Tobey Betthauser, University of Wisconsin

11:50 a.m. PET-based subtypes of AD. Renaud Lajoie, University of California, San Francisco

12:10 p.m. Neuropathologic evaluation of ADRD PET and fluid biomarker changes. Melissa Murray, Mayo Clinic Jacksonville

12:30 p.m. Integration of neuropathology and multimodal imaging data for clinical applications and studies in AD and ADRDs. Paul Yushkevich, University of Pennsylvania

12:50 p.m. PET as an endophenotype for genetic studies of AD/ADRD. Andy Saykin, Indiana University

1:10 p.m. Lunch Break

Session 3 | PET Imaging in ADRDs
The field faces urgent critical needs for the differential diagnosis of ADRDs, such as FTLD, Parkinson's disease/Lewy Body Disease, and LATE. Approaches capitalizing on disease-sensitive regional patterns of hypometabolism have sown promise, and PET tracers for the detection of proteinopathies associated with ADRDs--like non-AD tauopathies, alpha synucleinopathy, and TDP-43 proteinopathy--are ongoing, but face challenges associated with the coexistence of pathologies and the heterogenous molecular/supramolecular structures of proteinaceous aggregates.

1:40 p.m. Cryo-EM structures of amyloid filaments: Considerations for PET imaging tracers in neurodegenerative diseases. Benjamin Ryskeldi-Falcon, Medical Research Council, UK

2:10 p.m. Overview of alpha-syn tracers and selective 4R, 3R tracers. Robert Mach, University of Pennsylvania

2:40 p.m. Overview of emerging tau tracers. Neil Vasdev, University of Toronto

3:10 p.m. Imaging of the pathologic heterogeneity associated with alpha-synucleinopathies with PET. Kejal Kantarci, Mayo Clinic Rochester

3:30 p.m. Exploiting FDG PET in Limbic-predominant age-related TDP43-encephalopathy. David Jones, Mayo Clinic Rochester

3:50 p.m. Synaptic PET imaging in AD/ADRD. Barbara Bendlin, University of Wisconsin.

4:10 p.m. Day 1 Panel Discussion

4:40 p.m. Closing Remarks and Adjournment of Day 1

Day 2 (Thursday, March 13)

Session 4 | Neuroinflammation
Translational studies have veered radiochemist towards targeting pathophysiological processes involved in neurodegeneration, particularly, neuroinflammation. While a few such tracers have been introduced in clinical studies, and have potential to unveil histopathological changes across diseases, their performance has been unsatisfactory, and novel ligands are emerging that show promise to detect oxidative stress or selectively target inflammatory astrocytes or microglia.

9:30 a.m. Overview of immune activation in AD. David Morgan, Michigan State University

10:00 a.m. Imaging glia and neuroinflammation in AD. Pedro Rosa-Neto, UT Southwestern and McGill University

10:20 a.m. Neuroinflammation: Focus on astroglial markers. Victor Villemagne, University of Pittsburgh

10:40 a.m. CSF-1R as a promising PET imaging target. Ansel Hillmer, University of Michigan

11:00 a.m. TSPO PET tracers-utility in early-onset dementia and insights from clinical trials. Belen Pascual, Houston Methodist

11:20 a.m. Immunological profiles in AD/ADRD and their correlation to PET measures of AD/ADRD. Maura Malpetti, University of Cambridge

11:50 a.m. Integration of MRI brain connectivity with PET tau/inflammation to inform disease pathophysiology. Julie Ottoy, Sunnybrook Research Institute

12:10 p.m. Panel Discussion

12:40 p.m. Break

Session 5 | Emerging Tracers and Future Opportunities
Several tracers are under evaluation for use in humans to detect other processes that are thought to be involved in AD/ADRDs, such as, synaptic health, mitochondria function, chromatin regulation, myelinzation, microtubule stability, proteostasis, and lipid metabolism, to name a few. Emerging tracers have the potential to illuminate the biology of dementia and inform mechanistic hypothesis driving novel therapeutic/preventative interventions.

1:10 p.m. Neurotransmitter system PET tracers: applications in AD/ADRD. Gwenn Smith, Johns Hopkins University

1:30 p.m. Potential utility of mitochondrial complex 1 PET imaging in neurodegenerative diseases. Sarah Berman, University of Pittsburgh

1:50 p.m. Emerging targets in AD/ADRD: an overview of new tracers under evaluation in humans. Steven Liang, Emory University

2:20 p.m. Other biological processes we should monitor in AD. What are we missing? David Morgan, Michigan State University

2:50 p.m. From click chemistry to precision neuroscience. Hartmuth Kolb, Enigma Biomedical

3:20 p.m. Panel Discussion| How do we choose a good target for PET tracer development? What are the promises, challenges and constraints? Chairs: Julie Price, Massachusetts General Research Institute, and Elizabeth Mormino, Stanford University

Panelists:

• Hartmuth Kolb
• Steven Liang
• Robert Mach
• Tharick Pascoal
• Neil Vasdev

3:50 p.m. Wrap-Up and Closing Remarks