A new biomarker model could sharpen forecasts of disease progression years before symptoms begin.
Why This Matters
For people living with Alzheimer’s disease and their families, one of the hardest questions is: “How fast will this progress?” Current biomarkers can identify Alzheimer’s-related changes well before symptoms appear, but predicting when memory and thinking problems will begin remains difficult.
Now, researchers funded by the National Institutes of Health have identified a new type of biomarker in the blood that may change that. Small loops of genetic material called circular RNAs (circRNAs) appear to be more dynamic than amyloid plaques, reflecting recent brain activity. Elevated levels of certain circRNAs nearly tripled a person’s risk of developing Alzheimer’s symptoms, suggesting they could serve as an early warning system.
The possible value reaches beyond forecasting. Identifying people who are close to developing symptoms could help researchers choose the right participants for clinical trials and judge more clearly whether a treatment delays cognitive decline.
What the Study Found
The research, published in Nature Medicine, analyzed blood data from more than 1,200 people across multiple independent cohorts. The team, led by Dr. Carlos Cruchaga at Washington University School of Medicine in St. Louis, identified a set of 34 circRNAs associated with Alzheimer’s disease. They then built predictive models based on these circRNAs and compared them to models based on pTau217, the leading clinical blood biomarker for Alzheimer’s.
When identifying Alzheimer’s pathology, the circRNA model performed comparably to—and in the discovery data better than—the pTau217 model. It also outperformed pTau217 at predicting progression to symptomatic Alzheimer’s. The levels of these circRNAs appeared to diverge from normal roughly two to four years before symptom onset. The findings were then tested in two independent cohorts.
These results suggest that circRNAs may provide a more complete picture of the disease’s trajectory. As Dr. Cruchaga notes, patients treated with amyloid-removing therapies can become pTau negative but still have Alzheimer’s. Circular RNAs might offer a broader view of the disease biology, potentially helping monitor treatment response.
How to Interpret the Findings
This is early research, not a test people can request today. The study found an association between circRNA levels and Alzheimer’s progression; it did not show that circRNAs cause the disease. Larger prospective studies must now test how reliably the model performs when used to forecast future patients.
The study’s strength lies in its use of multiple independent cohorts and its comparison to an established biomarker. However, the predictive models were developed and tested in specific groups, and their real-world performance may vary. The authors themselves are working with commercial partners to develop clinical assays, indicating that translation to practice will take time.
For now, the result is a meaningful advance in forecasting research. If it holds up, circRNAs could help doctors and families understand the likely timing of symptom onset. It does not yet change current diagnostic or treatment recommendations.
Practical Next Steps
The practical takeaway is clarity about what this study can—and cannot—do. The research points toward a future forecasting tool, while the authors work with commercial partners on clinical assays. It does not replace a medical evaluation, and no consumer version of the test is currently available.
Anyone noticing persistent changes in memory or thinking can bring a written list of examples, medications, and questions to a medical appointment. That conversation uses tools available now; the circRNA model belongs to the next stage of Alzheimer’s research.
Three things to remember
- Circular RNAs in blood may predict Alzheimer’s symptom onset.
- They outperform pTau217 in forecasting disease progression.
- Test not yet available; more research needed.
Source
This analysis is based on New Alzheimer’s blood test may tell when symptoms are around the corner from NIH News Releases. Read the original report for full context.
Health note: The biomarker model is not a clinical test and still needs prospective validation in larger cohorts.