A new blood test under development may do more than detect Alzheimer’s disease — it could help predict when symptoms are likely to appear. According to a new National Institutes of Health (NIH)-funded study, small pieces of genetic material circulating in the blood may provide an earlier and more accurate warning that memory and thinking problems are approaching.

The findings could eventually help doctors identify people who are most likely to benefit from emerging Alzheimer’s treatments and improve the way clinical trials are conducted. Current blood tests for Alzheimer’s disease primarily detect proteins linked to amyloid plaques—abnormal clumps of protein that build up in the brain and are considered one of the disease’s defining features. While these tests can accurately identify Alzheimer’s-related changes, they often become positive many years, or even decades, before symptoms such as memory loss begin.

As a result, they provide limited information about when a person is likely to develop cognitive impairment, a decline in memory, thinking and reasoning abilities. Researchers believe a new type of biomarker may fill that gap. A biomarker is a measurable substance in the body that provides information about health or disease. The new study focused on circular RNAs (circRNAs), small loops of genetic material that help regulate how genes function. Unlike amyloid plaques, which accumulate slowly over time, circRNAs appear to reflect more recent changes occurring in the brain.

Researchers at Washington University School of Medicine analyzed blood samples from more than 1,200 people across several independent research groups. They identified 34 circRNAs that were consistently associated with Alzheimer’s disease. The researchers found that blood tests based on these circRNAs performed about as well as today’s leading Alzheimer’s blood biomarker, known as pTau217, in identifying people with Alzheimer’s-related brain changes. However, the new markers showed a major advantage when predicting future disease progression.

People with elevated levels of the 34 circRNAs had nearly three times the risk of developing Alzheimer’s symptoms compared with those who had lower levels. The researchers also found that these RNA changes appeared approximately two to four years before symptoms developed, making them a potentially valuable tool for identifying individuals who are approaching the earliest stages of the disease.

The findings were confirmed in two separate groups of participants, strengthening confidence in the results.