Blood-based biomarker discovery points to early-stage Alzheimer’s test

New research from the University of California San Diego is suggesting high levels of a certain blood-based biomarker may serve as an early warning sign of Alzheimer’s disease, two years before symptoms develop. The preliminary study has yet to be verified in larger cohorts of patients.

“Several known changes associated with Alzheimer’s disease usually show up around the time of clinical diagnosis, which is a little too late,” says lead on the new study, Sheng Zhong from UC San Diego Jacobs School of Engineering. “We had a hunch that there is a molecular predictor that would show up years before, and that’s what motivated this study.”

The research utilized a new method of sequencing RNA in blood samples, called SILVER-SEQ. Blood samples taken from 35 elderly subjects over a 15 year period were analyzed. A little less than half of the subjects were diagnosed with Alzheimer’s at the beginning of the study, nine remained healthy across the entire period, while 11 were classified as “converters” – developing Alzheimer’s symptoms as the 15 year period progressed.

The study homed in on a particular biomarker that seemed to rise in levels a couple of years before symptoms appeared in the “converters”. It seems overproduction of a type of RNA, called exRNA, by the PHGDH gene, correlated with the subsequent development of Alzheimer’s symptoms. High initial PHGDH exRNA levels were also noted in the subjects already diagnosed with Alzheimer’s.

Only one subject displayed rising PHGDH exRNA levels without subsequently developing Alzheimer’s disease. That subject died before the 15 year study period completed, so it is unclear whether they would have ultimately developed the disease or not.

“This is a retrospective study based on clinical follow-ups from the past, not a randomized clinical trial on a larger sample size,” says co-first author on the study Zixu Zhou, explaining the limitations of the research. “So we are not yet calling this a verified blood test for Alzheimer’s disease. Nevertheless, our data, which were from clinically collected samples, strongly support the discovery of a biomarker for predicting the development of Alzheimer’s disease.”

A number of blood tests are currently being developed in the hope of finding a way to diagnose Alzheimer’s disease before neurodegenerative symptoms appear. Many of these tests focus on detecting traces of amyloid and tau, the two proteins seen as responsible for the damage associated with the disease.

This new study offers a novel indication that circulating exRNAs can offer insights into brain-specific gene activity. The researchers suggest this is an important new area of biomarker study, as genetic expression changes may predate accumulations of tau and amyloid, offering clues to the earliest stages of the disease.

“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,” says Edward Koo, another researcher working on the study. “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 new research was published in the journal Cell Reports.

Source: UC San Diego

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