Elevated levels of an enzyme called PHGDH in the blood of older adults could be an early warning sign of Alzheimer’s diseaseaccording to a study led by the University of California in San Diego (USA) that provides new evidence on this “promising” marker.
By analyzing brain tissue, the researchers observed a trend consistent with their earlier findings: Expression levels of the gene responsible for PHGDH production are systematically higher in adults with different stages of Alzheimer’s, even in the early stages before cognitive symptoms manifest.
The researchers are led by Sheng Zhong and Xu Chen and the research is published in Cell Metabolism. The new study builds on earlier work by Zhong and his team that first identified PHGDH as a potential blood biomarker of Alzheimer’s, reports a statement from the University of California.
The researchers had analyzed blood samples from older adults and found a marked increase in the expression of the PHGDH gene in Alzheimer’s patients as well as in healthy individuals, approximately two years before of being diagnosed with the disease.
The results were promising and the scientists wanted to know whether this increase could be related to the brain; in their new study they show that this is indeed the case.
“It is exciting that our earlier discovery of a blood biomarker is now corroborated with brain data,” said Zhong: “We now have strong evidence that the changes we observe in human blood are directly correlated with changes in the brain in Alzheimer’s disease. Alzheimer’s”.
Post-mortem brain research
The researchers analyzed genetic data collected from postmortem human brains of subjects from four different research cohortseach of them made up of between forty and fifty individuals aged 50 or over.
The subjects were Alzheimer’s patientsso-called asymptomatic individuals (people with no cognitive problems and no diagnosis of Alzheimer’s, but whose post-mortem brain scans showed early signs of disease-related changes) and healthy controls.
The results showed a consistent increase in PHGDH activity among Alzheimer’s patients and asymptomatic individuals in all four cohorts compared to healthy controls.
In addition, the expression levels were higher the more advanced there was disease, a trend that was also seen in two different mouse models.
The findings also warn about the use of dietary supplements containing the amino acid serine as a remedy for this disease.
Since the PHGDH is a key enzyme in serine productionthe increased expression of PHGDH found in Alzheimer’s patients suggests that the rate of serine production in the brain is also increased and therefore taking more serine may not be beneficial, the researchers warn.
It is likely that serine production is increased in this disease, contrary to what other groups claim, the university stresses.
“Anyone who wants to recommend or take serine to mitigate Alzheimer’s symptoms I should be careful” summarizes Riccardo Calandrelli, another of the signatories.
Looking ahead, a biotech company co-founded by Zhong, called Genemo, is working on developing a blood test for PHGDH pfor early detection of this disease.