A simple blood test may one day tell doctors not only whether a person has Alzheimer’s disease, but also when memory problems are likely to begin.
That is the exciting possibility raised by a new study published in Nature Medicine.
Researchers found that small loops of genetic material called circular RNAs, or circRNAs, may provide an earlier and more accurate warning that symptoms are about to appear.
Alzheimer’s disease is the most common cause of dementia. It slowly damages brain cells and affects memory, thinking, language, and everyday activities. Scientists know that harmful amyloid plaques can build up in the brain many years, and sometimes even decades, before people notice memory problems.
Current blood tests can detect these plaques, making them useful for diagnosing Alzheimer’s disease. However, they cannot accurately tell doctors when symptoms will actually begin. This makes it difficult to decide when to start treatment or who should join clinical trials.
The new research offers a possible solution. Scientists from Washington University School of Medicine in St. Louis studied more than 1,200 people from several independent research groups.
They measured levels of circular RNAs in blood samples. Unlike ordinary RNA, which carries instructions for making proteins, circular RNAs form closed loops that are more stable in the bloodstream. Researchers believe these molecules reflect more recent changes taking place inside the brain.
The team identified 34 circular RNAs that were closely linked with Alzheimer’s disease. When these RNAs were combined into a prediction model, they identified people with Alzheimer’s disease almost as well as pTau217, one of today’s best blood biomarkers.
The biggest surprise came when the researchers looked at future disease progression. The circRNA test was much better than pTau217 at predicting who would soon develop Alzheimer’s symptoms.
Changes in these RNAs appeared around two to four years before noticeable memory decline. People with higher levels of the identified circRNAs had nearly three times the risk of developing symptoms.
The researchers believe this could help doctors identify patients who are entering the earliest stages of cognitive decline. Earlier identification could allow treatments to begin sooner, when they may work best. It could also help researchers recruit the right participants for clinical trials testing new Alzheimer’s medicines.
Another advantage is that circRNAs may continue to provide useful information even after patients receive modern treatments that remove amyloid plaques.
Some people become negative on amyloid-related blood tests after treatment but still have Alzheimer’s disease. The new RNA markers may give doctors a broader picture of what is happening inside the brain.
The research team is now working with commercial partners to develop practical blood tests that hospitals and clinics could eventually use. Before that can happen, additional studies will be needed to confirm the results in larger groups of people.
This is a large, carefully designed study that included more than 1,200 participants and multiple independent patient groups, making the findings more reliable than many early biomarker studies.
The results suggest circRNAs may predict symptom onset better than current blood tests. However, these tests are still experimental and are not yet available for routine medical care. Future clinical studies will determine whether they improve diagnosis and patient treatment in real-world practice.
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