Researchers at the University of California San Diego have discovered that elevated levels of an enzyme called PHGDH in the blood of older adults could serve as an early warning sign of Alzheimer’s disease.
This enzyme, which plays a critical role in producing the amino acid serine, was found to be more active in the brains of people with Alzheimer’s, even in the earliest stages before cognitive symptoms appear.
In their study, the scientists analyzed brain tissue from individuals at various stages of Alzheimer’s disease. They observed that the gene responsible for producing PHGDH was consistently more active in those with Alzheimer’s compared to healthy individuals.
This pattern held true even in people who had no cognitive symptoms but whose brain tissue showed early signs of Alzheimer’s-related changes.
This suggests that PHGDH could be a useful biomarker for detecting Alzheimer’s disease early, potentially even before any symptoms manifest.
The findings also raise concerns about the use of serine supplements as a treatment for Alzheimer’s disease. Serine, an amino acid produced in the body with the help of PHGDH, is often marketed as a supplement to boost memory and cognitive function.
However, since the study found increased PHGDH activity in Alzheimer’s patients, it suggests that the production of serine in the brain may already be elevated in these individuals. As a result, taking additional serine might not be beneficial and could even be counterproductive.
This research builds on a previous study by the same team, where they identified PHGDH as a potential blood biomarker for Alzheimer’s disease.
The earlier findings were promising, leading the researchers to investigate whether the elevated enzyme levels in the blood could be traced back to the brain.
Their current study confirms this link, showing that the increased PHGDH expression in the brain is indeed reflected in the blood.
To reach these conclusions, the researchers analyzed genetic data from post-mortem brain samples of individuals aged 50 and older. These individuals were part of four different research groups, each consisting of 40 to 50 people.
The groups included Alzheimer’s patients, asymptomatic individuals (those without cognitive problems but with early Alzheimer’s-related brain changes), and healthy controls.
Across all four groups, the researchers consistently found higher PHGDH levels in both Alzheimer’s patients and asymptomatic individuals compared to healthy controls.
The more advanced the disease, the higher the PHGDH levels, a trend also seen in two different mouse models of Alzheimer’s.
Furthermore, the study found a direct correlation between cognitive decline and PHGDH levels. Individuals with worse cognitive test scores had higher levels of PHGDH in their brains.
This finding challenges the idea that serine supplements, which some believe could help treat or prevent Alzheimer’s by boosting brain function, are beneficial.
While some researchers have suggested that Alzheimer’s patients may have reduced PHGDH expression and thus might benefit from increased serine intake, the data from this study suggests the opposite: that PHGDH expression is actually elevated in Alzheimer’s, and serine production may already be higher than normal.
Given these findings, the researchers urge caution regarding the use of serine supplements for Alzheimer’s disease.
They suggest that instead of reducing PHGDH expression, the enzyme’s activity is actually increased in Alzheimer’s, calling into question the effectiveness of serine supplements for treating the disease.
Clinical trials are currently underway to test the impact of serine on cognitive decline, but this study’s results indicate that more research is needed to fully understand the relationship between serine, PHGDH, and Alzheimer’s.
The study was led by Sheng Zhong and his team and was published in the journal Cell Metabolism. These findings highlight the complexity of Alzheimer’s disease and the need for careful consideration when developing and recommending treatments for it.
As researchers continue to explore the underlying mechanisms of the disease, this study provides a valuable insight into the role of PHGDH and its potential as an early indicator of Alzheimer’s.
If you care about brain health, please read studies about vitamin D deficiency linked to Alzheimer’s and vascular dementia, and blood pressure problem at night may increase Alzheimer’s risk.
For more information about brain health, please see recent studies about antioxidants that could help reduce dementia risk, and epilepsy drug may help treat Alzheimer’s disease.
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