Alzheimer’s biomarker causes a warning about serine supplements that boost the brain

SAN DIEGO, California – Serine supplements claim to help increase brain function and sharpen your thinking skills. Many people take these over-the-counter products to help prevent or even treat dementia. Now, researchers at UC San Diego suggest that this amino acid may contribute to the onset of dementia.

“Anyone who wants to recommend or take serine to alleviate Alzheimer’s symptoms should be careful,” study co-author Riccardo Calandrelli, an associate researcher at UCSD, warns in a university statement.

Led by Sheng Zhong, a professor of bioengineering at the Jacobs School of Engineering at UC San Diego, and Xu Chen, a professor of neuroscience at the UC San Diego School of Medicine, the research focuses on an enzyme called PHGDH in the blood. Researchers report that a group of older adults with various stages of Alzheimer’s disease, even the earliest stages before they show noticeable cognitive symptoms, share a great similarity: consistently higher levels of gene expression. which encodes PHGDH.

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

How does this connect to serine supplements?

PHGDH is a key enzyme in serine production. The fact that researchers observed consistent PHGDH expression in samples taken from dead Alzheimer’s patients suggests that there was probably an equally high rate of serine production in the brain while they were alive. Taking extra serine may not be beneficial, researchers warn.

These latest findings are based on previous work by Professor Zhong’s team that initially focused on PHGDH as a possible indicator of dementia. This study looked at blood samples collected from older adults and finally found a sharp increase in PHGDH gene expression among Alzheimer’s patients specifically, as well as healthy participants approximately two years before the diagnosis of Alzheimer’s. .

For this new research, the study authors wanted to establish whether this increase is related to the brain. The results add more evidence than is possible.

“It’s exciting that our previous discovery of a blood biomarker is now corroborated by brain data,” says Professor Zhong. “We now have strong evidence that the changes we see in human blood are directly correlated with changes in the brain in Alzheimer’s disease.”

Alzheimer’s patients show more PHGDH expression

The researchers analyzed genetic data from post-mortem human brains from four groups. They included patients diagnosed with Alzheimer’s, people with no notable cognitive impairment, and no diagnosis of Alzheimer’s, but whose post-mortem brain tests showed early signs of Alzheimer’s and healthy controls. Each group consisted of 40 to 50 individuals, all 50 years of age or older.

Compared with healthy controls, Alzheimer’s patients and “asymptomatic individuals” showed a steady increase in PHGDH expression. It is important to note that expression levels appeared to be higher the more advanced the disease. The team even saw this trend in two additional mouse models of Alzheimer’s disease.

The study authors also compared the PHGDH expression levels of each subject with their scores on two different clinical trials: The dementia assessment scalewhich measure a person’s memory and cognitive abilities, and Staging of vomit, which assesses the severity of Alzheimer’s disease based on brain pathology. Indeed, the worse a person scores on these tests, the higher the PHGDH expression in their brain.

“The fact that the level of expression of this gene is directly correlated with both a person’s cognitive ability and the pathology of the disease is remarkable,” explains Professor Zhong. “Being able to quantify these two complex metrics with a single molecular measure could make it much easier to diagnose and monitor the progression of Alzheimer’s disease.”

Change of opinion on supplements

Returning to serine, other scientists have theorized that PHGDH expression is actually reduced in Alzheimer’s disease, so taking serine supplements could help fight Alzheimer’s. Clinical trials are currently underway testing serine treatments for older adults with cognitive impairment.

However, the authors of this study believe exactly the opposite. Based on their data, which show a consistently high rate of PHGDH expression in Alzheimer’s patients, serine production is likely to increase due to dementia.

From now on, researchers are looking for new ways to analyze how the change in PHGDH gene expression may or may not change the different outcomes of the disease.

The findings appear in the journal Cellular metabolism.

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