A new NIH-funded study finds that elevated circular RNAs in blood may predict Alzheimer’s symptoms years in advance, outperforming current blood tests in forecasting disease progression.
Elevated levels of specific circular RNAs in the blood nearly tripled the risk of developing Alzheimer’s disease symptoms, according to a study funded by the National Institutes of Health (NIH). The research suggests these molecules are more sensitive to the onset of symptoms than traditional biomarkers, according to an NIH release.
While current blood tests for Alzheimer’s disease can detect markers of amyloid plaques decades before cognitive impairment, they are not highly informative regarding how the disease will progress, according to the NIH. This new research identifies a set of 34 circular RNAs that may predict when symptoms will begin.
“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,” says Richard Hodes, MD, director of the National Institute on Aging, in a release.
Circular RNAs vs Traditional Biomarkers
Unlike amyloid plaques, which accumulate slowly in the brain, circular RNAs are dynamic and reflect recent brain activity, according to the researchers. Carlos Cruchaga, PhD, the study’s corresponding author and a researcher at the Washington University School of Medicine, previously linked these molecules in the brain to dementia severity and sought to determine if the same associations existed in the blood.
The research team analyzed blood data from more than 1,200 individuals across multiple independent cohorts. They identified 34 circular RNAs associated with Alzheimer’s disease. In predictive models, these markers identified individuals with Alzheimer’s pathology with similar accuracy to pTau217, which is currently the leading clinical blood-based biomarker for the disease, according to the study.
Predicting Disease Progression
The circular RNA model outperformed the pTau217 model in predicting future disease progression. The 34 markers were stronger predictors of a patient’s transition to symptomatic Alzheimer’s, with levels appearing to diverge from normal approximately two to four years prior to the onset of symptoms, according to the NIH.
These findings may provide a foundation for tests that help clinicians identify candidates for treatments and monitor patient response, particularly for therapies targeting 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,” says Cruchaga in a release.
Researchers are currently working with commercial partners to develop clinical assays for blood-based circular RNAs, according to the NIH.
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