SV2A PET as a Biomarker of Synaptic Density

The Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium (BC) has launched a project that signals a paradigm shift in our methods to image the brain. Using advances in PET (positron emission topography) technology, the project will focus on measuring the integrity of synapses—tiny gaps that connect neurons and communicate information to the brain. Loss of these synapse connections strongly correlates with cognitive decline in Alzheimer’s disease (AD). A new imaging tool to track this biological indicator of disease progression and of patient response to therapeutic interventions would be a catalyst in the development of clinically effective treatments for AD.

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PET scans use a radioactive tracer to image normal and abnormal activity in many different organs. This technique is currently used to track the buildup of amyloid and tau proteins, two markers that serve as early indicators of Alzheimer’s disease but are not directly related to the biological underpinnings of cognitive loss. Recently, a PET tracer has been developed to bind to the synaptic vesicle glycoprotein 2A (SV2A), a protein located in neural synapses widely distributed throughout the brain. SV2A provides an opportunity to view the density of synapses and their decline. Studies using this PET tracer have demonstrated reduced SV2A binding in specific regions of the brain in Alzheimer’s patients, yet the biological basis of the alterations in SV2A is not well understood. The FNIH study seeks to thoroughly validate the SV2A PET tracer as a biomarker that can be used to measure therapeutic interventions in clinical trials and accelerate development of better treatments.

This three-year, $5.5M project brings together key stakeholders to advance our knowledge of the biological underpinnings of SV2A and the interpretation of the SV2A PET signal. Project partners include three institutes from the National Institutes of Health, 10 industry and nonprofit partners, individual donors, and four academic partners and service providers. This project will be an important first step toward a more expanded use of this important new biomarker to diagnose and treat other challenging neurodegenerative and neuropsychiatric diseases that affect the function and density of synapses, such as frontotemporal degeneration, schizophrenia spectrum disorder, major depressive disorder, and autism spectrum disorder. Building on more than two decades of commitment to finding solutions for AD, the FNIH is privileged to bring together these talented and diverse stakeholders dedicated to precision medicine and brain health.

Public-sector partners

• National Institute on Aging
• National Institute of Mental Health
• National Institute of Neurological Disorders and Stroke

Academic partners and service providers

• Banner Health
• University of Edinburgh
• University of Gothenburg
• Yale University

Private-sector partners

• AbbVie
• Alkermes, Inc.
• Alzheimer’s Drug Discovery Foundation
• Biogen MA Inc.
• BrightFocus Foundation
• Genentech, a member of the Roche Group
• Janssen Research & Development, LLC
• Sage Therapeutics Inc
• Sanofi
• Takeda Pharmaceutical Company Limited