Alzheimer’s biomarker warns of brain-boosting serine compounds

SAN DIEGO, California. – Serine supplements have been shown to help boost brain function and thinking ability. Many people take these over-the-counter products to prevent or even treat mental disorders. Researchers at the University of San Diego now believe that this amino acid can contribute to the development of dementia.

“Anyone who wants to offer or receive a serine to alleviate Alzheimer’s symptoms should be careful,” warns Riccardo Calandrelli, author of the first study, a UCSD researcher, in a university release.

The study, led by Sheng Zhong, a bioengineering professor at UC San Diego Jacobs School of Engineering, and Xu Chen, a professor of neurology at UC San Diego Medical School, focused on an enzyme in the blood called PHGDH. Report a group of older people with different stages of Alzheimer’s disease, and even the earliest stages before the onset of noticeable cognitive symptoms shared another great similarity: consistently high levels of PHGDH encoding gene expression.

In other words, high levels of PHGDH in the blood may serve as a clear warning sign for Alzheimer’s.

How does this relate to serine supplements?

PHGDH is a key enzyme in serine production. Researchers have consistently observed PHGDH expression in samples from patients who died of Alzheimer’s disease, indicating that they had a similarly high rate of serine production in the brain during their lifetime. Taking extra serine may not be helpful, researchers warn.

These latest findings Zhong’s team initially set PHGDH to zero as an indicator of possible dementia. The study analyzed blood samples from elderly people and finally found a sharp increase in PHGDH gene expression among patients with Alzheimer’s disease, as well as healthy participants two years before the diagnosis of Alzheimer’s.

For this new study, the study authors wanted to determine whether this increase was related to the brain. The results add another piece of evidence that this is possible.

“It is very interesting that the previous discovery of our blood biomarker was confirmed by data from the brain,” said Prof. Zhong says. “Now we have strong evidence that changes in human blood are directly related to changes in the brain in Alzheimer’s disease.”

Patients with Alzheimer’s are more likely to show PHGDH expression

Researchers analyzed four groups of genetic information from the human brain after death. These included patients diagnosed with Alzheimer’s, those with undiagnosed but not cognitive problems, and those without Alzheimer’s disease, post-mortem brain tests that showed early Alzheimer’s, and healthy people. Each group consists of 40-50 people, all 50 and older.

Compared with healthy controllers, Alzheimer’s patients and “asymptomatic people” showed a steady increase in PHGDH expression. Importantly, the level of expression seemed to be higher as the disease progressed. The team also saw this trend in two additional mouse models of Alzheimer’s disease.

The study authors also compared each subject’s PHGDH expression levels with scores on two different clinical trials: Dementia rating scalea measure of human memory and cognitive ability and Marriage staging, it assesses the severity of Alzheimer’s disease based on brain pathology. Of course, the worse a person scores on these tests, the higher the PHGDH expression in the brain.

“Surprisingly, the level of expression of this gene is directly related to both the cognitive abilities of the person and the pathology of the disease,” said the professor. Zhong explains. “The ability to determine an equal number of these complex parameters with a single molecular measurement can greatly simplify the diagnosis and monitoring of the progression of Alzheimer’s disease.”

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Turning to serine, other scientists have theorized that PHGDH expression in Alzheimer’s disease is actually reduced, so taking serine compounds can help fight Alzheimer’s. Currently, clinical trials are testing serine therapy for the elderly who are struggling with cognitive decline.

However, the authors of this study believe that the exact opposite is true. Based on their data showing consistently high rates of PHGDH expression in Alzheimer’s patients, serine production may be increased due to dementia.

Researchers are moving forward and looking for new ways to analyze whether changes in PHGDH gene expression can alter the outcome of any disease.

The results appear in the log Cell metabolism.

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