Impact of semaglutide on amyloid positivity

Summary

The lack of effective treatments for dementia remains one of the key challenges to modern medicine and society. Its leading cause is Alzheimer’s disease (AD), a condition where proteins (called amyloid and tau) build up in the brain causing inflammation and loss of nerve cells. Importantly, we now know that this process begins decades before first symptoms of dementia appear offering an opportunity to stop it in its tracks with the right treatment.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a class of medication used for the treatment of type 2 diabetes and obesity. They have been shown to reduce the risk of heart attack, stroke, and renal disease in people with diabetes, and in animal experiments they have also been found to affect the mechanisms thought to be involved in AD.

In this study we will examine the effects of oral semaglutide (a GLP-1 RA tablet) on the build-up of AD proteins, on brain inflammation and on thinking ability in people thought to be at high risk of developing AD. We will recruit people with high levels of amyloid protein in the brain (thought to be the key factor in triggering AD) to a clinical study in which we will give them either oral semaglutide or a dummy tablet for one year. We will ask them to come in for head scans which detect the build-up of tau protein and brain inflammation before they start taking the drug, and again after one year, to see whether those given semaglutide tablets do better compared with those given dummy tablets.