A new study done by researchers at the University of California San Diego shows that overproduction of RNA by the Phosphoglycerate Dehydrogenase (PHGDH) gene in aging people could be an early warning sign for Alzheimer’s disease. The PHGDH gene is responsible for producing RNA and other proteins that are important for brain development. As we age, the PHGDH gene slows down RNA and protein production.
Dr. Sheng Zhong, professor of bioengineering at the University of California (UC) San Diego Jacobs School of Engineering and co-lead study author says, “Several known changes associated with Alzheimer's disease usually show up around the time of clinical diagnosis, which is a little too late. We had a hunch that there is a molecular predictor that would show up years before, and that's what motivated this study.”
The researchers believe that the overproduction of a type of RNA called exRNA could be an early indicator of Alzheimer’s disease. Zhong and his colleagues developed a technique called SILVER-SEQ to sequence thousands of exRNA profiles from 35 people who were at least 70 years old. The scientists monitored the participants for up to 15 years prior to death. Of the 35 participants, 15 had Alzheimer’s, 11 were initially healthy and developed Alzheimer’s later in the study (referred to as converters), and 9 were healthy. The researchers made the diagnoses by analyzing the subjects’ brains post-mortem.
The scientists found that about two years before the converters were clinically diagnosed with Alzheimer’s, they had increased exRNA production, and the average levels of exRNA were higher in the Alzheimer’s patients.
Dr. Edward Koo, professor of neuroscience at the UC San Diego School of Medicine and co-study author says, “If our results can be replicated by other centers and expanded to more cases, then it suggests that there are biomarkers outside of the brain that are altered before clinical disease onset and that these changes also predict the possible onset or development of Alzheimer's disease. If this PDGDH signal is shown to be accurate, it can be quite informative for diagnosis and even treatment response for Alzheimer's research." The study is published in the journal, Current Biology.