Alzheimer’s biomarker sparks warning about brain-boosting serine supplements

SAN DIEGO, Calif. — Serine supplements claim to help boost brain function and sharpen thinking skills. Many people take these over-the-counter products to help stave off or even treat dementia. Now, researchers from UC San Diego suggest this amino acid may actually contribute to the onset of dementia.

“Anyone looking to recommend or take serine to mitigate Alzheimer’s symptoms should exercise caution,” cautions co-first study author Riccardo Calandrelli, a research associate at UCSD, in a university release.

Led by Sheng Zhong, professor of bioengineering at the UC San Diego Jacobs School of Engineering, and Xu Chen, a professor of neurosciences at UC San Diego School of Medicine, the research focuses on an enzyme called PHGDH in the blood. Researchers report a group of older adults all dealing with various stages of Alzheimer’s disease, even the earliest stages before noticeable cognitive symptoms show themselves, shared one big similarity: Consistently higher expression levels of the gene coding for PHGDH.

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

How does this connect to serine supplements?

PHGDH is a key enzyme in the production of serine. The fact that researchers observed consistent PHGDH expression in samples taken from deceased Alzheimer’s patients suggests there was probably a similarly high rate of serine production in their brains while alive as well. Taking additional serine may not be beneficial, researchers warn.

These latest findings build off of earlier work conducted by Prof. Zhong’s team that initially zeroed in on PHGDH as a possible dementia indicator. That study analyzed blood samples collected from older adults, ultimately discovering a steep increase in PHGDH gene expression among Alzheimer’s patients specifically – as well as healthy participants roughly two years before their Alzheimer’s diagnosis.

For this new research, study authors wanted to establish if this increase links back to the brain. The results add further evidence that it can.

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

Alzheimer’s patients display more PHGDH expression

Researchers analyzed genetic data from post-mortem human brains across four groups. They included patients diagnosed with Alzheimer’s, people with no noticeable cognitive issues and no Alzheimer’s diagnosis but whose post-mortem brain analyses showed early signs of Alzheimer’s, and healthy controls. Each group consisted of 40 to 50 individuals, all 50 and older.

In comparison to the healthy controls, Alzheimer’s patients and “asymptomatic individuals” displayed a consistent increase in PHGDH expression. Importantly, expression levels appeared to be higher the more advanced the disease. The team even saw this trend in two supplementary mouse models of Alzheimer’s disease.

Study authors also compared each subject’s PHGDH expression levels to their scores on two distinct clinical tests: The Dementia Rating Scale, which measure a person’s memory and cognitive abilities, and Braak staging, which rates Alzheimer’s disease severity based on brain pathology. Sure enough, the worse a person scored on these tests, the higher the expression of PHGDH in their brain.

“The fact that this gene’s expression level directly correlates with both a person’s cognitive ability and disease pathology is remarkable,” Prof. Zhong explains. “Being able to quantify both of these complex metrics with a single molecular measurement could potentially make diagnosis and monitoring progression of Alzheimer’s disease much simpler.”

Changing opinions on supplements

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

Still, this study’s authors believe the exact opposite. Based on their data, which shows a consistent high rate of PHGDH expression in Alzheimer’s patients, the production of serine likely increases due to dementia.

Moving forward, researchers are looking for new ways to analyze how changing PHGDH gene expression may or may not changes various disease outcomes.

The findings appear in the journal Cell Metabolism.

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  1. With findings like this you have to be cautious about drawing a concrete conclusion like Serine causes Alzheimer’s. It could be people who’ve dealt with it in their family are more inclined to take such supplements, knowing that they may be more susceptible, and therefore have higher blood levels of those micro nutrients.

  2. Well, taking serine versus phosphatidylserine (PS) are two very different things. Most knowledgeable nutritional professionals recommend the latter in some of their brain and nootropic protocols, and post-stroke (along with GPC). The PS is generally incorporated in-whole into the neuronal membranes, which is the intention to increase their integrity and fluidity. It does not raise free serine in the brain to my knowledge.

    Also, this press release seems to be trying to make a bunch of hay about one enzyme in the brain (extremely reductionist in itself) that may contribute to making serine be in excess in AD. However, what is the enzyme is being up regulated in AD patients intentionally by the body because it requires more serine to combat it? To me, while interesting and may prompt more deeper research, right mow it seems like more classic myopic PhD researcher stuff turned into flashy headlines.

  3. What supplements have or are Serine booster? Science is interesting but hardly ‘news you can use.’

  4. I don’t believe anything coming out of Chinese so called scientist

  5. Depends on what form of serine that’s being talked about. For example:

    Genetics and Molecular Research (2015)
    Effect of phosphatidylserine on memory in patients and rats with Alzheimer’s disease

    From the Abstract

    “…In AD patients, vocabulary and picture matching scores in the two treatment groups increased after treatment (P < 0.05). Moreover, the scores in the treated group were significantly greater than the control group (P< 0.05)."

  6. Maybe the body, recognizing that something is wrong, tries to compensate by increasing serine production…

  7. It seems to me that research must clarify its findings about serine vs phosphatidylserine. And, if taking phosphatidylserine increases the progression and severity of Alzheimers, then the public and nutritional professionals should be informed. Though Alpha GPC has been touted as an excellent supplement, a recent study indicated that if you take it long term, there is a nearly 50% risk of increasing your chance of stroke. That is a significant finding and should be taken seriously especially by those of us who do take supplements long term. In the best interests of their readership, I would encourage to follow up with additional results about and recommendations for the use of phosphatidylserine. Thank you. DrBob

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