A new National Institutes of Health (NIH)-funded study has identified a novel blood test utilizing circular RNAs (circRNAs) that may predict the imminent onset of Alzheimer's disease (AD) symptoms with greater accuracy than existing diagnostic methods. Researchers found that elevated levels of specific circRNAs in the blood nearly tripled a patient's risk of developing symptoms, indicating these molecules are more sensitive to symptom onset than traditional AD biomarkers.
Current AD blood tests reliably diagnose the disease by detecting amyloid plaques, but they often produce positive results decades before cognitive impairment, offering limited insight into disease progression. Richard Hodes, M.D., director of NIH's National Institute on Aging (NIA), said, "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."
Unlike slowly accumulating amyloid plaques, circRNAs are dynamic, reflecting recent brain activity. Carlos Cruchaga, Ph.D., and his team at Washington University School of Medicine, St. Louis, analyzed blood data from over 1,200 individuals, identifying 34 circRNAs associated with AD. Their predictive model outperformed the leading clinical blood-based biomarker, pTau217, in forecasting progression to symptomatic AD, with levels diverging from normal approximately two to four years before symptom onset.
These findings are foundational for developing tests that could help clinicians identify candidates for novel treatments and monitor their response, particularly for amyloid-targeting drugs. Cruchaga said, "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." Researchers are now working with commercial partners to develop clinical assays for blood-based circRNAs.