Synaptic Health

The EMI's Synaptic Health theme is investigating the role of synapses in people with, or at risk of, dementia. These critical connections between brain cells are damaged early in the development of many different forms of cognitive decline. Understanding synaptic health may be key to better treatments in the future. 

Background

Synapses are the connections which carry information between brain cells (neurons). They are critical for thinking, memory, decision making, perception and movement. Loss of and damage to synapses have been implicated in the development of Alzheimer's disease and other forms of dementia. They are an early indicator of the development of these conditions, with damage caused by the aggregation of proteins (tau and amyloid), neuroinflammation, and brain cells' response to other stressors including vascular changes.

DPUK's Synaptic Health theme is revealing not only how synaptic changes lead to cognitive impairment, but also how these changes can be measured in humans. To measure the loss of synapses in people with Alzheimer's disease and other forms of dementia, we are testing cutting-edge brain scanning methods and analysis of blood and cerebrospinal fluid (the fluid around the brain, known as CSF). New types of brain scan to measure synapses and cognitive physiology have been developed by DPUK's leading research partners in universities and the pharmaceutical industry, including Janssen (Johnson & Johnson) and AstraZeneca. This research will identify new markers of synaptic health and function that are anticipated to play an important role in testing new treatment possibilities in early-stage clinical trials.

Workstreams

The Synaptic Health theme has two major workstreams. The first assesses the relationship between the number and function of synapses. We measure the number and distribution of these connections using a ligand (a biological molecule 'dye') that targets the synaptic vesicle glycoprotein 2A (SV2A). This protein is found on all synapses – more specifically on the brain cell that is sending information (called pre-synaptic). The ligand is measured by position emission tomography (PET) imaging.

The function of the brain, for information processing and memory, will be measured using a different type of scan called magnetoencephalography (MEG). MEG scanning records the activity across the whole brain 1,000 times per second. In addition, synaptic fragments that are released into CSF will be measured to assess how they relate to the loss of synapses as seen on brain scans. The complementary information from brain imaging and CSF analysis provides extra validation for the new research methods.

The second workstream looks at the potential for scalable blood based measures of synaptic health, enabling studies of diverse dementias, over time and in relation to other risk factors like inflammation and vascular change.

Get involved

If you are a researcher and would like to know more about the Synaptic Health theme and how your institution might collaborate or access data, please contact Professor James Rowe or check the Data Portal.

Theme objectives

1. To assess whether the synaptic vesicle glycoprotein 2A (SV2A, detected by PET ligand) in people with Alzheimer's disease (including mild cognitive impairment) correlates with clinical decline, with sufficient sensitivity and reliability to support clinical trials.

2. To assess whether the products of synaptic breakdown in CSF reflect the density and degree of loss of synapses as measured by PET.

3. To assess MEG And EEG markers of Alzheimer’s disease and other dementias, as a function of synapse loss.