Synapses—the tiny gaps between neurons that communicate information in the brain—are potential targets for developing biomarkers to measure brain health and cognitive function. Synaptic density and function loss correlates strongly with the cognitive decline in the brains of patients with Alzheimer’s disease. However, Researchers lack a reliable biomarker to track synaptic loss and dysfunction in living subjects; a synapse-specific biomarker could be used to follow the progression of cognitive decline and measure the potential clinical stabilization or reversal of Alzheimer’s disease with treatment.
|Beta-Amyloid Plaques and Tau in the Brain
Credit: National Institute on Aging, NIH
Current methods for measuring synaptic density involve invasive spinal taps, which lack information about specific areas of cognitive decline. A leading candidate for more precise measurement is the synaptic vesicle glycoprotein 2A (SV2A), a protein in neural synapses widely distributed throughout the brain. Monitoring and measuring SV2A allows for viewing synaptic density and decline. However, changes to SV2A expression, distribution, and binding in the brains of patients with Alzheimer’s disease are poorly understood.
Positron emission tomography (PET) scans use a radioactive tracer to image various organs’ normal and abnormal activity. This technique is currently used to track the buildup of amyloid and tau proteins; these two markers serve as early indicators of Alzheimer’s disease. Still, they are not directly related to the biological underpinnings of cognitive loss. Recently, a PET tracer has been developed to bind with SV2A. Studies using this PET tracer have demonstrated reductions in SV2A binding in specific brain regions in Alzheimer’s disease patients. The FNIH study seeks to validate the SV2A PET tracer as a biomarker to track disease progression and measure disease-altering interventions in clinical trials. The goal is to determine a new imaging tool that can be used to develop clinically effective treatments for Alzheimer’s disease.
- National Institute on Aging
- National Institute of Mental Health
- National Institute of Neurological Disorders and Stroke
- Alkermes, Inc.*
- Alzheimer’s Drug Discovery Foundation*
- Biogen MA Inc.*
- BrightFocus Foundation*
- Genentech, a member of the Roche Group*
- Invicro, LLC*
- Janssen Research & Development, LLC*
- Sage Therapeutics Inc*
- Takeda Pharmaceutical Company Limited*
Academic Partners and Service Providers
*Provides financial or in-kind support for this program
- Understand the biology of SV2A tracer binding within the synapse
- Compare SV2A PET in the brains of a healthy control group to those with mild cognitive impairment and Alzheimer’s disease, both in-vivo and post-mortem
- Confirm, through robust analytical validation, whether SV2A PET signals reflect the synaptic density
- Demonstrate the usefulness of SV2A PET as a treatment response biomarker in clinical trials
FNIH Announcement (October 4, 2022):