Alzheimer’s Disease: Dopamine Treatment Offers New Hope

A patient with Alzheimer's disease being pushed in a wheelchair in Tokyo, Japan.

Researchers continue to study and look for effective treatments for Alzheimer’s disease. This degenerative brain disorder affects tens of millions of people worldwide and causes a gradual yet severe decline in their thinking, behavioral, and social skills. Recently, researchers at the RIKEN Center for Brain Science (CBS) in Japan published the results of their studies on another potential treatment for the disease.

Conducting their studies on lab mice, the researchers discovered that treating the mice’s brains with dopamine helped the organs break down harmful plaques linked to Alzheimer’s. While the researchers have yet to conduct clinical trials to determine how to replicate similar results in human brains, the discovery of this method offers an exciting new approach to treating this aggressive disease.

Building Up Enzymes And Breaking Down Plaques

In their August 6 paper in the journal Science Signaling, the researchers explained how plaques, or hardened clumps, of peptides called amyloid-β or beta-amyloids clog up the brain and may contribute to the progressive cognitive impairment associated with Alzheimer’s disease. Though scientists have developed many therapies that focus on preventing or reducing plaque buildup, they’ve faced challenges trying to make these therapies safer with patients with Alzheimer’s. Thus, the researchers in this study aimed to find a safe and effective method for breaking up these plaques to help patients recover some of their lost cognitive functions.

The researchers decided to focus on how to increase the levels of neprilysin, an enzyme the brain uses to break down amyloid-β plaques, in the brain. Based on previous experiments with mice, they knew that certain genetic manipulations would allow the mice’s brains to produce excess amounts of neprilysin and that enzyme helped improve the mice’s memories. Since similar modifications wouldn’t work for humans, the researchers set out to find a natural way to boost the enzyme.

Boosting Mice’s Brains With Dopamine

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Photo by RODRIGO BUENDIA/AFP via Getty Images.

The research team screened many molecules to discover which ones could naturally upregulate the amount of neprilysin in the mice’s brains. They eventually narrowed their search down to hormones produced in the hypothalamus. During testing on brain cells cultured in a dish, they discovered that the reward-reinforcing neurotransmitter dopamine increased levels of the enzyme and reduced levels of the peptide. Following that discovery, they began experimenting with giving dopamine to mice that had an Alzheimer’s-like disease.

Using a DREADD (Designer Receptors Exclusively Activated by Designer Drugs) system, the team first tiny designer receptors into the dopamine-producing neurons inside the mice’s brains. Then they added a designer drug called levodopa or L-DOPA, a precursor molecule of dopamine that’s often used to treat Parkinson’s, into the food they gave the mice. After eight weeks of this treatment process, the mice had higher levels of neprilysin and lower levels of beta-amyloid plaques in their brains; after three months, these mice showed much higher scores on memory tests than untreated mice did.

Moving Onto The Human Mind

While these experiments have shown positive effects on breaking down Alzheimer’s-related plaques in mice, the researchers note that there might be some complications in figuring out how to boost neprilysin production in human brains compared to mice ones. For one reason, giving patients with Alzheimer’s neprilysin pills or injections wouldn’t work because the enzyme can’t enter the brain from the bloodstream. For another, though L-DOPA is used in humans to treat symptoms of Parkinson’s disease, the drug can also cause severe side effects in patients as well.

Since their results on mice’s brains were so promising, the researchers now want to explore how their approach could benefit human patients with Alzheimer’s. Thus, their next step is to determine how dopamine regulates neprilysin in the brain and how to effectively deliver extra neprilysin to the human brain. By determine these two things, the researchers hope to discover a cleaner, safer, and more effective treatment method that can be initiated at the preclinical stage of the disease.

Final Thoughts

Alzheimer’s disease is an aggressive disease that impacts the health and lives of millions of people around the world. Researchers continue to study the disease, its development, and its effects in order to find effective ways to treat and reverse its effects. This recent study shows that dopamine boosts the levels of the enzyme neprilysin to break apart plaques and combats Alzheimer’s-related cognitive impairment in mice.

The study’s researchers are now looking to discover how dopamine regulates neprilysin in the brain so they can identify how to boost the levels of that enzyme in human brains as well. Though the researchers still need to conduct clinical trials on humans to test potential treatment methods, their discovery of dopamine’s beneficial effects on memory recovery represents a promising new approach to fighting Alzheimer’s disease.

Disclaimer: This article is intended simply to provide information. It does not replace the medical advice of a physician. Please speak with your doctor if you have any questions or concerns.

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