New radiotracer allows scientists to count synapses in people’s brains

When it comes to processing information in the human brain, much of the work happens at the organ’s 100 trillion or so synapses, the gaps between neurons through which the cells communicate.

Researchers now report a way to measure the density of synapses in people using positron emission tomography, or PET (Sci. Transl. Med. 2016, DOI: 10.1126/scitranslmed.aaf6667). The method could help elucidate the mechanisms behind diseases in which people lose synapses, such as epilepsy, Alzheimer’s disease, and possibly depression, the scientists say.

Measuring synaptic density in living people had not been possible previously, say Sjoerd J. Finnema and Richard E. Carson of Yale University, who led the team. Scientists have instead been making such measurements in tissue collected during brain surgery or from deceased patients.

Finnema, Carson, and colleagues designed a radiolabeled molecule that can be detected via PET and binds to synaptic vesicle glycoprotein 2A (SV2A), a protein found at synapses.

The team confirmed that the PET tracer, dubbed [¹¹C]UCB-J, targets SV2A in people’s brains, in part, by blocking its accumulation using an epilepsy drug known to bind the synaptic protein. And in three people with epilepsy, PET scans with the tracer revealed reduced synaptic density at the sites of known brain lesions in the patients.

Kathryn A. Davis, a neurologist who studies epilepsy at the University of Pennsylvania, wonders if the technique could help locate brain lesions in epilepsy patients for whom standard imaging techniques have failed to identify such sites.

And John Q. Trojanowski, also at UPenn, is excited by the method’s prospects for studying the loss of synapses in the progression of Alzheimer’s and other neurodegenerative diseases. “The communities studying these diseases,” he says, “have been awaiting a ligand like this for many years.”