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A new study suggests that semaglutide, a drug commonly used to treat diabetes, may help protect the brain from the effects of Alzheimer’s disease. Researchers found that semaglutide reduced inflammation in the brains of genetically modified mice that mimic Alzheimer’s disease and improved their memory performance. The findings, published in the journal Neuroscience, add to growing evidence that diabetes medications may offer benefits for neurodegenerative diseases, though more research is needed to understand how these drugs exert their effects.
Semaglutide is a medication sold under brand names such as Ozempic and Wegovy, commonly used to treat type 2 diabetes and obesity. It belongs to a class of drugs known as glucagon-like peptide-1 receptor agonists, which help regulate blood sugar and appetite. In recent years, scientists have discovered that these drugs may have additional benefits beyond metabolic control, including potential protective effects in neurodegenerative diseases like Alzheimer’s.
Alzheimer’s disease gradually damages nerve cells in the brain, leading to memory loss and cognitive decline. This deterioration is linked to the buildup of toxic proteins, chronic inflammation, and impaired energy metabolism in brain cells. Some studies suggest that semaglutide may help by reducing brain inflammation and preventing cell damage, but the precise mechanism is not yet fully understood. The new study aimed to investigate how semaglutide affects brain inflammation and memory function in a well-established mouse model of Alzheimer’s disease.
To test semaglutide’s effects, the researchers used a well-established mouse model of Alzheimer’s disease known as APP/PS1/tau transgenic mice. These mice carry genetic mutations that cause the buildup of amyloid plaques and tau tangles, the two main hallmarks of Alzheimer’s disease. The study also included a group of normal, healthy mice for comparison.
The mice were divided into four groups: a control group of normal mice given a placebo, a group of Alzheimer’s model mice given a placebo, a group of normal mice given semaglutide, and a group of Alzheimer’s model mice treated with semaglutide. The researchers administered semaglutide at a dose of 25 nanomoles per kilogram every other day for 30 days. After the treatment period, the mice underwent behavioral tests to assess their memory and learning abilities. The researchers also examined brain tissue to measure levels of inflammation and amyloid plaque buildup.
The results showed that semaglutide improved both short-term and long-term memory in the Alzheimer’s model mice. In a test called the Y-maze, which measures spatial working memory, untreated Alzheimer’s model mice performed significantly worse than normal mice. However, those treated with semaglutide showed improved memory performance, nearly matching the healthy control mice. Similarly, in the Morris water maze, a test that assesses long-term spatial memory, semaglutide-treated mice found the hidden platform more quickly than untreated Alzheimer’s model mice.
On a biological level, semaglutide reduced the amount of amyloid plaque in the hippocampus, a brain region crucial for memory. The researchers also found that semaglutide lowered levels of inflammatory molecules such as interleukin-1 beta and tumor necrosis factor-alpha, which are known to contribute to brain cell damage. At the same time, semaglutide increased levels of anti-inflammatory molecules such as interleukin-4 and interleukin-10, which help protect brain cells.
One of the key findings was that semaglutide appeared to change the behavior of microglia, the brain’s immune cells. In Alzheimer’s disease, microglia become overly activated and release harmful inflammatory substances. Semaglutide encouraged microglia to shift from a pro-inflammatory state, known as the M1 type, to an anti-inflammatory state, known as the M2 type. This transformation is thought to reduce brain damage and promote healing.
To further investigate how semaglutide affects inflammation, the researchers conducted additional experiments using cultured microglial cells. When these cells were exposed to amyloid beta, a toxic protein linked to Alzheimer’s, they became inflamed and started releasing harmful substances. However, when the cells were pretreated with semaglutide, they produced fewer inflammatory molecules and were less likely to undergo cell death.
Interestingly, semaglutide did not appear to increase the number of glucagon-like peptide-1 receptors in the brain, which are the drug’s primary target in diabetes treatment. This suggests that semaglutide may enhance the sensitivity of existing receptors rather than increasing their quantity.
Although the findings are promising, the study has several limitations. First, the research was conducted in mice, and it is unclear whether the same effects will be seen in humans. While semaglutide has been shown to cross the blood-brain barrier, its precise effects on human brain inflammation and memory remain to be fully tested.
Second, the study focused primarily on microglia, but other brain cells, such as astrocytes, also play a role in neuroinflammation and may be influenced by semaglutide. Future research should investigate whether semaglutide affects other types of brain cells and how these changes contribute to neuroprotection.
Finally, while this study focused on short-term treatment effects, Alzheimer’s disease progresses over many years. Future studies should examine whether long-term semaglutide treatment can slow cognitive decline in aging animals and, ultimately, in people with Alzheimer’s disease.
Semaglutide is currently being tested in large-scale clinical trials for Alzheimer’s disease, and if the results are positive, it could become one of the first medications to treat both diabetes and neurodegeneration. These findings add to the growing body of evidence suggesting that drugs designed for metabolic disorders might also hold promise for brain health.
The study, “Semaglutide promotes the transition of microglia from M1 to M2 type to reduce brain inflammation in APP/PS1/tau mice,” was authored by Zhao-Jun Wang, Wei-Na Han, Shi-Fan Chai, Yan Li, Chao-Jing Fu, Chen-Fang Wang, Hong-Yan Cai, Xin-Yi Li, Xiao Wang, Christian Hölscher, and Mei-Na Wu.
