Although about one in 14 people over 65 have Alzheimer’s disease, there is still no cure and no way to prevent the disease from progressing. But a recent study may bring us a step closer to preventing Alzheimer’s. The test, which was conducted on animals, found that a specific molecule can prevent the accumulation of a toxic protein known to cause Alzheimer’s in the brain.
Since 1906, researchers have known that amyloid plaques are one of the causes of Alzheimer’s disease. These plaques are stubborn, sticky deposits that accumulate in our brain and contain a protein called beta-amyloid. This protein has been the focus of many studies and we have learned a lot about what it does and how it causes nerve cell death.
Beta-amyloid first attacks the communication networks between our nerve cells (called synapses) and then suffocates nerve cells. This damage to nerve cells induced by amyloid is what contributes to the symptoms of Alzheimer’s disease. Currently, there is no drug that can change the amount of amyloid plaque that accumulates in the brain or prevent this accumulation from happening.
Beta-amyloid comes from a protein called amyloid precursor protein (APP), which resides throughout our bodies – not just in the brain. The APP protein family is involved in a number of biological functions, from the production of other proteins to the control of communication between nerve cells.
However, when larger APP molecules are broken down by the body into smaller fragments, they can take two paths. One of these routes is not linked to the disease, while the other route has been shown to raise beta-amyloid levels. If we look at the path that leads to Alzheimer’s disease, scientists have identified an enzyme known as gamma secretase as a key player in converting APP to beta-amyloid.
Scientists spent a lot of time trying to reach the secretase range to prevent the sticky build-up of beta-amyloid that forms the plaques. But despite this perception, our efforts to inhibit the actions of gamma secretase have largely failed, with some tests indicating that inhibition may increase the rate of decline in brain function.
Experimental molecule
However, a recent study took a different approach than the previous ones. Instead of trying to shut down the secretase range, they sought to decrease its activity. To do this, the researchers needed to generate new molecules that would change the activity of gamma secretase and offer protection against the formation of beta-amyloid deposits in the brain.
The team generated three compounds of interest while working at very low concentrations – something that is vital for making new drugs. The researchers then sought to take one of these compounds further and test it on an animal model of Alzheimer’s disease.
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To do this, they used mice that were altered to generate more beta-amyloid – thus exhibiting some of the signs of Alzheimer’s disease. The mice were treated for three months with daily administration of the compound. The result was a reduction in the amount of beta-amyloid in the brain in half. Although other studies have produced similar results in animal models, the results of this study are significant because this compound could be used not only to treat dementia, but also to prevent it.
They also noticed other changes in the brains of mice treated with this molecule. The molecule dampened the reaction of the brain’s immune cells, the microglia. While these cells are important for brain health, they can also be harmful when overactivated – which is what happens with Alzheimer’s disease. This shows that the benefits of the drug can be twofold.
Where to go next?
The next step in bringing this compound to people living with dementia is to conduct clinical tests to validate the results of the laboratory. This is often the point where the lab’s work fails to deliver on its promise.
Although researchers have done a lot of research to give this compound a chance of success, the success rate of drugs targeting our brain is about 6%. Previous gamma secretase modulators have not progressed to becoming medications due to adverse effects reported by participants.
But the molecule tested in this study has the advantage of being more powerful, which ends up making less of the molecule necessary to have an effect on users. If it were to enter clinical trials, researchers would be looking for a variety of results to prove a positive result, such as improving a person’s memory test performance. The tests may also involve brain scans to monitor structural changes and track beta-amyloid deposits in the brain.
The signs are positive for this molecule to move forward, but the transition from the laboratory to the clinic has seen many molecules fail to live up to expectations. However, it adds another molecule for testing, which is needed as researchers continue to seek relief for people living with Alzheimer’s and for those awaiting a diagnosis.