Poster Number: NR 14 - Initial Experience with PET Imaging of Synaptic Density (SV2A) in Alzheimer's Disease: A New Biomarker for Clinical Trials?

Abstract

Introduction: The ability to measure synaptic density in vivo would accelerate the development of disease-modifying treatments for Alzheimer's disease (AD). Positron Emission Tomography (PET) imaging of glucose metabolism with 18F-fluorodeoxyglucose (18F-FDG) has been widely used to measure neuronal activity and to track the progression of AD. However, 18F-FDG is not a direct biomarker of synaptic density and may be affected by stimulation, medication, and blood glucose. Therefore, tracers for new molecular targets are needed to directly monitor synaptic density. One suitable target is the synaptic vesicle glycoprotein 2 (SV2), an essential vesicle membrane protein. One of its isoforms, SV2A, is ubiquitously expressed in virtually all synapses and is involved in regulation of synaptic trafficking. Abnormal neurotransmission was reported in mice lacking SV2A (Crowder KM, et al, Proc Natl Acad Sci U S A. 1999;96:15268). Thus, SV2A imaging could provide a highly useful indicator of synaptic density in AD. We recently developed 11C-UCB-J, a PET tracer for quantitative SV2A imaging in vivo and carried out the first-in-human studies (Finnema SJ, et al. Sci Transl Med. 2016;8:348).