A National Institutes of Health-funded study has identified a potential new blood test that researchers say could more accurately predict when Alzheimer's disease symptoms are likely to develop, offering a possible tool for identifying patients on the verge of cognitive decline.

The research found that elevated levels of certain circular RNAs, or circRNAs, in the blood nearly tripled a person's risk of developing Alzheimer's symptoms, a news release said. Researchers said the molecules appear to be more sensitive to the onset of symptoms than current blood-based Alzheimer's biomarkers.

Current Alzheimer's blood tests diagnose the disease by detecting markers of amyloid plaques, one of the disease's hallmarks. While those tests can identify Alzheimer's pathology decades before cognitive impairment begins, researchers said they provide limited information about how quickly a patient's disease will progress.

The new findings lay the groundwork for a blood test that could potentially predict when symptoms are about to appear.

"In a clinical setting, being able to identify patients on the verge of symptom onset would be invaluable. Having this information could help us select the right patients for clinical trials and better determine which treatments are effective at preventing cognitive decline," Richard Hodes, M.D., director of NIH's National Institute on Aging, said in the release.

Unlike amyloid plaques, which build up gradually in the brain, circRNAs are more dynamic and reflect more recent brain activity.

In an earlier study, Carlos Cruchaga, Ph.D., and colleagues at Washington University School of Medicine in St. Louis linked circRNAs found in the brain to dementia and the severity of Alzheimer's-related brain disease. To determine whether those molecules could serve as a practical clinical marker, the researchers examined circRNAs circulating in blood.

The team analyzed blood samples from more than 1,200 people across multiple independent cohorts and identified a group of 34 circRNAs associated with Alzheimer's disease. Predictive models based on those circRNAs successfully identified people with Alzheimer's pathology and performed similarly to models using pTau217, the leading blood-based clinical biomarker for Alzheimer's disease.

However, researchers found the circRNA model significantly outperformed the pTau217 model in predicting future disease progression. The 34 circRNAs were stronger indicators of whether patients would develop symptomatic Alzheimer's disease. Additional experiments suggested circRNA levels begin to differ from normal about two to four years before symptoms appear. Similar results were observed in samples from two independent cohorts.

Researchers said the findings could help pave the way for blood tests that identify patients who may benefit from emerging Alzheimer's treatments and help clinicians monitor how well those therapies are working, particularly medications that target amyloid plaques.

"Patients being treated with novel Aβ-removal therapies, can become pTau negative but still have Alzheimer's disease. These circular RNAs may grant us a more complete perspective of someone's overall disease biology," said Cruchaga, the study's corresponding author.

Cruchaga said researchers are working with commercial partners to develop clinical blood tests based on circRNAs.

"It's nice to have good science and models, but we're ultimately doing this to help people," Cruchaga said.

NIH said it supported the research through National Institute on Aging grants R01AG064614, U01AG084514, R01AG078964, R01AG058501, R01AG071706, P30AG066444, R01AG064877, P30AG066444, P01AG03991 and P01AG026276 as well as National Institute of Neurological Disorders and Stroke grant P01NS131131.

According to NIH, the National Institute on Aging works to better understand aging and diseases associated with growing older with the goal of extending healthy and active years of life. More information is available at www.nia.nih.gov.

The National Institutes of Health, part of the U.S. Department of Health and Human Services, is the nation's primary federal agency for conducting and supporting basic, clinical and translational medical research on common and rare diseases. More information is available at www.nih.gov.