JUL 27, 2016 6:31 AM PDT

PET Scan to Visualize Synaptic Density in the Living Brain

WRITTEN BY: Cassidy Reich
Synapses are the connections between neurons that allow them to communicate with each other. When synapses become compromised and can no longer effectively communicate, they are lost, and brain function suffers. Synaptic density would be a great measure for diagnosis and for tracking neuropathology in certain diseases, but there is currently no way to look at synaptic density in the living brain. Evaluating synaptic density requires brain tissue from autopsy or surgical resection. However, scientists have developed a new radioligand for PET (positron emission tomography) scans that is capable of measuring synaptic density in the living brain.

There are ~100 trillion synapses in the human brain.
This research was recently published in Science Translational Medicine and described PET studies with a new radioligand that were conducted in non-human primates, healthy human subjects, and epileptic patients with mesial temporal lobe sclerosis.

Usually when measuring synaptic density in brain tissue, researchers will use an antibody against synaptophysin, a protein that is present in every single presynaptic vesicle. However, there is currently no radioligand that can be used for PET that binds to synaptophysin. The company UCB does have an antiepileptic drug, levetiracetam, that targets another synaptic vesicle protein, SV2A. A derivative of this drug, [11C]UCB-J, is the radioligand that was tested in these studies and has been shown to specifically bind to SV2A. SV2A, just like synaptophysin, is present in every synapse.

When they tested [11C]UCB-J in non-human primates, they saw a signal in gray matter and none in white matter, which makes sense. Gray matter consists of the axons and dendrites of neurons, i.e. where the synapses are, and white matter is the cell bodies of those neurons. To investigate the quantitative nature of their tracer, the scientists also cross-validated PET signals with post-mortem brain tissue analysis of SV2A protein levels in several brain regions.

Following non-human primate studies, [11C]UCB-J was tested in healthy human subjects and was found to be effective and had favorable kinetics. The real test was to do a PET scan with [11C]UCB-J in epileptic patients with mesial temporal lobe sclerosis. In patients with this condition, there is loss of synapses in the hippocampus in one hemisphere and the atrophy is also visible on MRI. With this new tracer, the scientists were able to visualize the loss in synaptic density in the hippocampus on the affected side compared to the unaffected side, and were also able to correlate the synapse loss with degree of atrophy.  


This is a crazy advancement for neuroimaging because synapse loss is present in so many neurological conditions and is also one of the pathological events in Alzheimer’s disease (AD) that closely tracks with cognitive decline. When neurons die, they die, and there is no getting them back. But it might be possible to reverse damage to the synapses which is the step that precedes neuronal loss in AD. Which this kind of imaging, it will be possible to monitor the effect of early interventions in AD on synaptic density, a measure that correlates with cognitive decline more so than other biological markers.

I have barely scratched the surface, and if you are interested, I strongly suggest looking at the original article in Science Translational Medicine and also this great write-up on AlzForum.
About the Author
Cassidy is a curious person, and her curiosity has led her to pursue a PhD in Pharmacology at the New York University Sackler Institute of Biomedical Sciences. She likes to talk about science way too much, so now she's going to try writing about it.
You May Also Like
MAR 24, 2022
Neuroscience
A Molecular Mechanism Underlying Long-Term Memory is Revealed
MAR 24, 2022
A Molecular Mechanism Underlying Long-Term Memory is Revealed
Dementia refers to memory loss that commonly accompanies aging, and the most common form of dementia is Alzheimer's dise ...
APR 18, 2022
Plants & Animals
Some Fish Species Can Count
APR 18, 2022
Some Fish Species Can Count
If someone asked you if fish could count, your response would probably be… probably not? Counting seems like an a ...
APR 21, 2022
Drug Discovery & Development
Antidepressants and Anti-epileptics During Pregnancy May Affect Infant Brain Development
APR 21, 2022
Antidepressants and Anti-epileptics During Pregnancy May Affect Infant Brain Development
Fetal exposure to a mother's antiepileptic or antidepressant medication may affect infant brain development. The cor ...
MAY 12, 2022
Neuroscience
Secondary Tasks in Interviews Help Identify Liars
MAY 12, 2022
Secondary Tasks in Interviews Help Identify Liars
Lying requires more cognitive energy than telling the truth. Working with this fact, researchers have found that the ext ...
MAY 16, 2022
Clinical & Molecular DX
Trial Underway for Alzheimer's Vaccine
MAY 16, 2022
Trial Underway for Alzheimer's Vaccine
Almost twenty years ago, researchers at the Ann Romney Center at Brigham and Women’s Hospital began researching th ...
MAY 20, 2022
Neuroscience
Suppressing Negative Memories Makes Them Fade Away
MAY 20, 2022
Suppressing Negative Memories Makes Them Fade Away
Actively suppressing negative experiences may help prevent intrusive thoughts and rumination. The corresponding study wa ...
Loading Comments...