Alzheimer's Biomarker Findings Cast Doubt on Dietary Supplement

Abstract

Genetic Engineering & Biotechnology NewsVol. 42, No. 6 News & AnalysisFree AccessAlzheimer's Biomarker Findings Cast Doubt on Dietary SupplementPublished Online:8 Jun 2022https://doi.org/10.1089/gen.42.06.04AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail KATERYNA KON/SCIENCE PHOTO LIBRARY/Getty ImagesScientists are still trying to understand how Alzheimer's disease (AD) is related to serine, which is known to modulate synaptic plasticity, and phosphoglycerate dehydrogenase (PHGDH), which is required for serine's synthesis. Although some researchers have suggested that a form of serine could serve as an AD therapeutic, other researchers have expressed doubts.The scientists with doubts include the researchers at the University of California, San Diego, led by neuroscientist Xu Chen and bioengineer Sheng Zhong. For these researchers, a key issue is whether PHGDH and serine expression levels rise or fall in AD. Two years ago, in Current Biology, the researchers reported that they had analyzed blood samples of older adults and found a steep increase in PHGDH gene expression in AD patients, and that the increase was evident in healthy individuals approximately two years before they were diagnosed with the disease.The results were promising, indicating that high blood levels of RNA produced by the PHGDH gene could serve as a blood biomarker for early detection of AD. To follow up on these results, the researchers investigated whether increases in PHGDH gene expression could be linked back to the brain. They measured PHGDH mRNA and protein levels in two mouse models of AD and in four human cohorts in AD brains compared to ageand sex-matched control brains.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 AD based on the brain's pathology).What did the scientists find? The answers appeared in Cell Metabolism, in an article titled, “PHGDH expression increases with progression of Alzheimer's disease pathology and symptoms.” The increases were found in experiments with mouse models of AD and/or tauopathy, and in analyses of genetic data collected from postmortem human brains.“PHGDH mRNA and protein levels,” the scientists reported, “are progressively increased in human brains with no, early, and late AD pathology, as well as in people with no, asymptomatic, and symptomatic AD.”“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 AD.”“The fact that this gene's expression level directly correlates with both a person's cognitive ability and disease pathology is remarkable,” Zhong added. “Being able to quantify both of these complex metrics with a single molecular measurement could potentially make diagnosing and monitoring the progression of AD much simpler.”The scientists also noted that in their work, they were careful to control for postmortem delay (PMD). “Considering that human PHGDH protein is sensitive to protease cleavage at room temperature,” the scientists wrote, “PMD-related protein degradation may explain the lower PHGDH levels” that were reported by another research team. In Cell Metabolism, the other team wrote, “Our findings … suggest oral L-serine as a ready-to-use therapy for AD.” In contrast, the team led by Chen and Zhong declared that oral L-serine “warrants precaution.”FiguresReferencesRelatedDetails Volume 42Issue 6Jun 2022 Information© 2022 by GEN PublishingTo cite this article:Alzheimer's Biomarker Findings Cast Doubt on Dietary Supplement.Genetic Engineering & Biotechnology News.Jun 2022.12-12.http://doi.org/10.1089/gen.42.06.04Published in Volume: 42 Issue 6: June 8, 2022PDF download