A Single Blood Test May Predict When Alzheimer’s Symptoms Will Begin

A few years ago, a clinical trial tested an anti-amyloid drug, solanezumab, to determine if it could prevent Alzheimer’s. The drug ultimately failed, but the trial offered participants the chance to learn if they had high levels of one of the disease’s defining proteins in their brain, beta-amyloid plaques.

Dr. Suzanne Schindler, a neurologist at Washington University in St. Louis, who helped run the trial, remembered the participants who learned they had plaques asking her: “How long do I have before I develop symptoms?” 

At the time, answering that question was impossible. Now, a new study published in Nature Medicine by Schindler and her colleagues shows that it may be possible to predict when someone will develop Alzheimer’s symptoms using a single blood test — with predictions accurate enough to guide clinical trial design.

The research was developed and launched by the Foundation for the National Institutes of Health, a not-for-profit established by Congress to bring together researchers, industry partners, and patients to advance medical research. 

While researchers have used amyloid and tau PET scans in the past to make these predictions, “this is the first time doing it with blood tests,” Schindler told Being Patient. Because blood tests are faster and cheaper, they could help researchers and drug companies identify healthy people likely to develop Alzheimer’s symptoms within a certain timeframe, making it easier to run trials for preventive treatments. 

A clock that predicts Alzheimer’s symptoms

Schindler and her colleagues analyzed multiple blood samples taken at least one year apart from 603 healthy older adults who were participating in one of two large longitudinal studies tracking their brain health over time. Compared to the general population, the participants in this study were well-educated and a higher proportion of them had the Alzheimer’s risk gene ApoE4.

They tracked a blood biomarker called %pTau-217 — a ratio of two forms of a tau fragment, pTau-217 and npTau-217 — which serves as a proxy measure of beta-amyloid and tau buildup in the brain. Once %pTau-217 hits a tipping point, it indicates that a person is positive for Alzheimer’s biomarkers in the brain. The analysis also accounted for the fact that not everyone who becomes positive for %pTau-217 goes on to develop symptoms. 

“As you get older, this window between becoming positive and developing symptoms gets smaller and smaller,” said Schindler. When someone hits the tipping point is the most important predictor of when they’d develop cognitive symptoms. 

An individual who became biomarker positive at age 60 had about 20.5 years until symptom onset, while one who became positive at 80 had 11.4 years. The researchers found they could make similar predictions with other blood biomarkers as well.

“There’s a significant error of plus or minus three years, which doesn’t sound great,” said Schindler. Still, she said, it matches the level of prediction we have for genetic forms of Alzheimer’s disease, where families are almost always guaranteed to develop the disease.

“We think that these models can be refined considerably so that we can get more accurate estimates if we add more blood biomarkers, imaging, and cognitive measures,” Schindler said.

Davide Cappon, director of neuropsychology at Tufts Medical Center, who wasn’t involved in the study, told Being Patient it would be interesting to include measures of vascular health, brain resilience, and other dementia-related protein plaques to improve the precision. 

Other factors, like whether they carried one or two copies of the Alzheimer’s risk gene ApoE4, sex, and educational attainment may affect when someone might hit %pTau-217 positivity. But they don’t affect how soon symptoms start after hitting that tipping point. 

Dr. Heather Whitson, a geriatrician who serves as director of the Duke Aging Center and co-director of the Duke/UNC Alzheimer’s Disease Research Center, who wasn’t involved in the study, told Being Patient that the study was important but more work is needed.

“While the clocks developed here could be important for use in clinical trials,” she said, “making these predictions apply to individual patients in patient care will need refinement to better reflect the population.” 

What’s next for Alzheimer’s clocks?

Using all their data, Schindler and her colleagues developed an app for researchers that could help them predict the probability participants will develop Alzheimer’s symptoms and when based on the results of different pTau-217 blood tests. These tools could be used to help develop even better predictors and help plan for more efficient trials of preventative treatments. 

“I could foresee this quickly becoming a really helpful tool for clinical trials and research,” Whitson said. Schindler and Whiston both emphasized that the tool is only for research and agreed with current guidelines that don’t support giving these blood tests to cognitively healthy people at the moment.  

With so much progress in the Alzheimer’s space, Schindler said, “In the not too distant future, it really may be possible to develop individualized estimates of symptom onset.”