Targeting PPAR, a receptor that plays a vital role in metabolic disorders, reversed signs of early Alzheimer’s in mice. The mice got a PPAR agonist (a drug that switches PPAR on) called DTMB for three months. Brain inflammation and amyloid-beta (the plaque protein) went down. Memory and thinking got better.
Summary: In recent years, researchers have started to see that Alzheimer’s shares many traits with other metabolic disorders. It appears that metabolic changes in the body upset microglia, the brain’s immune cells. That brings inflammation, then a buildup of amyloid-beta protein, and then Alzheimer’s. The new study in mice shows that PPAR agonists may help prevent and even reverse early Alzheimer’s. Already more than 6.5 million US adults live with Alzheimer’s. Even more worrying, the number keeps rising. Alzheimer’s causes not only early death but also years of disability. After more than a century of research, researchers still struggle with many questions about Alzheimer’s. It is hard to believe, but doctors know very little about it. They do not know what causes it. They do not even know much about how it progresses. That is why they cannot find a remedy that may prevent it or treat it well. Of course, they know that Alzheimer’s comes from a buildup of misfolded proteins, called amyloid and tau. But they still do not know why this happens or at what stage it starts. The causes remain unclear. This suggests that Alzheimer’s probably has many causes, like genes, aging, toxins, infection, and metabolic disorders. Some of these causes can be prevented, and some cannot. Alzheimer’s is rising at an alarming rate. So researchers think it is strongly tied to metabolic disorders. Metabolic disorders like diabetes are also rising at an alarming rate. That is why some experts call it “type 3 diabetes”. Now some researchers think metabolic disorders might be the main cause of Alzheimer’s. So cutting metabolic disorders may also help cut Alzheimer’s. Another key change in recent years is a shift in focus from neurons to glial cells. Glial cells are more common in the brain. They play a key role in the brain’s immune defense and inflammation. So researchers think they have been looking at the wrong cells all these years. They think glial cells go wrong because of metabolic changes in the body. That causes faulty proteins to build up, and then dementia. From studies in diabetes and other metabolic disorders, researchers know that peroxisome proliferator-activated receptors (PPAR) play a vital role in metabolic disorders. So researchers are looking for strong PPAR agonists, drugs that switch on these receptors. Researchers think PPAR agonists can help lower Alzheimer’s risk. In the new study, researchers began testing a new PPAR agonist called DTMB. This new chemical can calm brain inflammation. That cuts the buildup of amyloid and tau proteins in the brain. In lab tests in mice, researchers saw that DTMB lowers the inflammatory signals made by microglia, one of the most common immune cells in the brain. It appears that calming microglia can help significantly. It can slow or even stop the buildup of faulty proteins. That halts the chain reaction these misfolded proteins set off. 
In the study, feeding mice DTMB for three months could help reverse many signs of dementia. It could help improve memory and thinking. Researchers also found lower levels of amyloid-beta protein. And they found significantly less brain inflammation. Researchers think their study could be of significant value, because PPAR agonists are fairly simple drugs to make. Many drugs already used in clinics can act on PPAR. And many other molecules like DTMB are known to be quite good at it. So researchers need to keep studying this path.
Frequently asked questions
What is type 3 diabetes?
Type 3 diabetes is a name some experts use for Alzheimer’s disease. Alzheimer’s shares many traits with metabolic disorders. It is rising fast, right alongside diabetes. Some researchers now think metabolic disorders may be the main cause of Alzheimer’s. That is why the two are linked under one name.
What causes type 3 diabetes?
Metabolic changes in the body upset the brain’s glial cells. These cells run the brain’s immune defense and control inflammation. When they go wrong, microglia send out alarm signals. Then misfolded amyloid and tau proteins pile up, and dementia follows. Genes, aging, toxins and infection can also play a part. But the metabolic link is one you can change.
How can type 3 diabetes be prevented?
Some causes of Alzheimer’s can be prevented, and metabolic disorders are among them. Cutting down metabolic disorders such as diabetes may also cut down Alzheimer’s. Researchers are also testing drugs that act on PPAR, a receptor that plays a big role in metabolic disorders. The goal is to calm brain inflammation before bad proteins pile up.
What did the DTMB study in mice find?
Mice fed DTMB, a new PPAR agonist, for three months showed a reversal of many signs of early Alzheimer’s. Their memory and thinking got better. Amyloid-beta levels fell, and brain inflammation dropped significantly. PPAR drugs are fairly simple to make. So researchers see this as a path worth chasing.
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