Testing the effect of the diabetes drug Liraglutide in Alzheimer's disease

Lead Investigator: Dr Paul Edison
Institution: Imperial College London
Grant type: Project
Duration: 3 years
Amount: £338,525
Scientific Title: Effect of GLP-1 analogue, Liraglutide, on cerebral glucose metabolism and microglial activation in Alzheimer's disease.

What do we already know?

Recently, a connection between type 2 diabetes and Alzheimer's disease has been discovered; people with type 2 diabetes are much more likely to develop Alzheimer's disease than healthy people of the same age group.

Recently, a new compound that is like a naturally occurring protein called Glucagon-like peptide-1 (GLP-1) has been extensively studied; GLP-1 is produced in the intestine after eating and normalises blood glucose and increases blood glucose in cells.

A hallmark of Alzheimer's disease is the formation of plaques of a protein called amyloid forming within the brain. GLP-1 has previously been shown to reduce amyloid production and protect neurons (nerve cells) against nerve cell damage caused by amyloid. GLP-1 and other similar compounds have also been shown to have protective effects on the communication between nerve cells.

The compound that is similar to GLP-1, called Liraglutide, is currently used as a treatment for type 2 diabetes. Because it is like GLP-1, Liraglutide is very promising in the treatment of Alzheimer's disease and other conditions where nerve cell damage is present.

In this study, the researchers are going to test the effect of Liraglutide in the treatment of Alzheimer's disease patients, to see whether this new drug reduces brain inflammation and prevents neuronal damage using a type of brain scan called PET scan.

What does this project involve?

This study will involve people with Alzheimer's disease, performing PET scans at the start of the study and after one year. For the duration of the study, participants will receive injections of either the compound Liraglutide or a placebo, and comparisons on the amount of inflammation and levels of amyloid present within their brains will be made after one year of this drug treatment.

Brain scans will look at the amount of glucose used by cells within the brain and the levels of inflammation across the participants' brains. Spinal fluid will also be taken from participants who give permission, at the start of the trial and after one year, to measure the levels of the Alzheimer's disease hallmark proteins, amyloid and tau.

How will this benefit people with dementia?

This research will provide valuable information on how the GLP-1 like compound Liraglutide affects brain inflammation, brain glucose uptake, and spinal fluid amyloid and tau levels.

This will also give us pilot data about the safety of these drugs in people with Alzheimer's disease. In the event that Liraglutide causes reduction in brain inflammation and prevents rapid decline of brain glucose uptake, it provides a much stronger basis for a large multicentre clinical trial.

Alzheimer's disease is a disorder that arises as a result of many causes, and most of the interventions use agents that target a single mechanism or single protein. Removal of one biomarker may not resolve Alzheimer's disease, and therapy should target different factors. Liraglutide has shown multiple effects because of the unique nature of the compound.