Elevated levels of an enzyme called PHGDH in the blood of older adults could be an early warning sign of
Researchers led by Sheng Zhong, a 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, published their findings on May 3, 2022, in the journal Cell Metabolism.
The new study builds on earlier work by Zhong and colleagues that first identified PHGDH as a potential blood biomarker for Alzheimer’s disease. The researchers had analyzed blood samples of older adults and found a steep increase in PHGDH gene expression in Alzheimer’s patients, as well as in healthy individuals approximately two years before they were diagnosed with the disease.
The results were promising, and the researchers were curious if this increase could be linked back to the brain. In their new study, they show that this indeed is the case.
“It’s exciting that our previous discovery of a blood biomarker is now corroborated with brain data,” said Zhong. “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.”
The researchers analyzed genetic data collected from post-mortem human brains from subjects in four different research cohorts, each made up of 40 to 50 individuals 50 years and older. The subjects consisted of Alzheimer’s patients, so-called “asymptomatic” individuals (people without cognitive problems and without an Alzheimer’s diagnosis, but whose post-mortem brain analyses showed early signs of Alzheimer’s-related changes), and healthy controls.
The results showed a consistent increase in PHGDH expression among Alzheimer’s patients and asymptomatic individuals in all four cohorts compared to the healthy controls. Moreover, expression levels were higher the more advanced the disease. This trend was also observed in two different mouse models of Alzheimer’s disease.
The researchers also compared the subjects’ PHGDH expression levels with their scores on two different clinical assessments: the Dementia Rating Scale, which rates a person’s memory and cognitive ability, and Braak staging, which rates the severity of Alzheimer’s disease based on the brain’s pathology. The results showed that the worse the scores, the higher the expression of PHGDH in the brain.
“The fact that this gene’s expression level directly correlates with both a person’s cognitive ability and disease pathology is remarkable,” said Zhong. “Being able to quantify both of these…
Read More: Warning About Brain-Boosting Supplements After Alzheimer’s Disease Biomarker