MSGID: 1:317/3 62720193   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    Study of promising Alzheimer's marker in blood prompts warning about   
   brain-boosting supplements    
      
     Date:   
         May 3, 2022   
     Source:   
         University of California - San Diego   
     Summary:   
         Elevated levels of an enzyme called PHGDH in the blood of   
         older adults could be an early warning sign of Alzheimer's   
         disease. Researchers have consistently found high levels of PHGDH   
         expression in brain tissue and blood samples of older adults with   
         different stages of the disease.   
      
      
      
   FULL STORY   
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   Elevated levels of an enzyme called PHGDH in the blood of older adults   
   could be an early warning sign of Alzheimer's disease, and a study led by   
   the University of California San Diego provides new evidence to support   
   this claim. In analyzing brain tissue, researchers observed a trend   
   consistent with their previous findings in blood samples: expression   
   levels of the gene coding for PHGDH were consistently higher in adults   
   with different stages of Alzheimer's disease, even the early stages   
   before cognitive symptoms manifested.   
      
      
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   The findings also prompt caution against the use of dietary supplements   
   that contain the amino acid serine as a remedy for Alzheimer's   
   disease. Because PHGDH is a key enzyme in the production of serine, the   
   increased PHGDH expression found in Alzheimer's patients suggests that   
   the rate of serine production in the brain is also increased, and thus,   
   taking additional serine may not be beneficial, the researchers warned.   
      
   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 May 3 in 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 complex metrics with a single   
   molecular measurement could potentially make diagnosis and monitoring   
   progression of Alzheimer's disease much simpler."  The case against   
   serine The findings come with implications for serine supplements, which   
   are advertised to improve memory and cognitive function. The key player   
   responsible for making serine in the body is PHGDH. Some researchers have   
   proposed that PHGDH expression is reduced in Alzheimer's disease, and that   
   boosting serine intake could help with treatment and prevention. Clinical   
   trials are already underway to test serine treatments in older adults   
   experiencing cognitive decline.   
      
      
      
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   But with their data consistently showing increased PHGDH expression in   
   Alzheimer's, the researchers posit that serine production may likely be   
   increased in this disease, contrary to what some other groups claim.   
      
   "Anyone looking to recommend or take serine to mitigate Alzheimer's   
   symptoms should exercise caution," said co-first author Riccardo   
   Calandrelli, who is a research associate in Zhong's lab.   
      
   Next steps The researchers are looking to study how changing PHGDH gene   
   expression will affect disease outcomes. The approach could lead to new   
   therapeutics for Alzheimer's.   
      
   A San Diego-based biotechnology startup co-founded by Zhong, called   
   Genemo, is working to develop a PHGDH blood test for early detection of   
   Alzheimer's disease.   
      
      
   ==========================================================================   
   Story Source: Materials provided by   
   University_of_California_-_San_Diego. Original written by Liezel   
   Labios. Note: Content may be edited for style and length.   
      
      
   ==========================================================================   
   Journal Reference:   
      1. Xu Chen, Riccardo Calandrelli, John Girardini, Zhangming Yan,   
      Zhiqun Tan,   
         Xiangmin Xu, Annie Hiniker, Sheng Zhong. PHGDH expression increases   
         with progression of Alzheimer's disease pathology and symptoms. Cell   
         Metabolism, 2022; 34 (5): 651 DOI: 10.1016/j.cmet.2022.02.008   
   ==========================================================================   
      
   Link to news story:   
   https://www.sciencedaily.com/releases/2022/05/220503110518.htm   
      
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