Researchers at the University of California, San Diego, have discovered that high blood levels of RNA produced by the PHGDH gene could serve as a biomarker for early detection of Alzheimer’s disease.1 The work could lead to the development of a blood test to identify individuals who will develop the disease years before they show symptoms.

The PHGDH gene produces RNA and proteins that are critical for brain development and function in infants, children, and adolescents. As people get older, the gene typically ramps down its production of these RNAs and proteins.

The new study, led by Sheng Zhong, PhD, a professor of bioengineering at the UC San Diego Jacobs School of Engineering, in collaboration with Edward Koo, MD, a professor of neuroscience at the UC San Diego School of Medicine, suggests that overproduction of a type of RNA, called extracellular RNA (exRNA), by the PHGDH gene in the elderly could provide an early warning sign of Alzheimer’s disease.

“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,” Zhong says.

The discovery was made possible thanks to a technique developed by Zhong and colleagues that is sensitive enough to sequence tens of thousands of exRNAs in less than one drop of blood. The method, dubbed Silver-SEQ, was used to analyze the exRNA profiles in blood samples of 35 individuals aged 70 years and older who were monitored up to 15 years prior to death.

Read more from UC San Diego.

1. Yan Z, Zhou Z, Wu Q, Chen ZB, Koo EH, Zhong S. Presymptomatic increase of an extracellular RNA in blood plasma associates with the development of Alzheimer’s disease. Curr Biol. Epub ahead of print, March 26, 2020; doi: 10.1016/j.cub.2020.02.084.

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