A Simple Blood Test Can Predict Alzheimer’s Years Before Memory Loss

Scientists at Washington University School of Medicine in St. Louis have developed a new method that uses a single blood test to estimate when a person is likely to develop symptoms of Alzheimer’s disease. In a study published in Nature Medicine, the team reported that their model can predict the onset of Alzheimer’s symptoms within about three to four years. Such accuracy could help researchers develop faster and more targeted clinical trials for treatments to prevent the disease. Over time, this could also help identify individuals who would most benefit from early intervention.

Alzheimer’s Affects Millions of People Worldwide

In the US alone, more than 7 million people live with Alzheimer’s. The Alzheimer’s Association estimates that the cost of caring for people with Alzheimer’s and other dementias will reach nearly $400 billion by 2025. Although there is no cure yet, tools that can predict the onset of symptoms could help delay or reduce their impact.

“Our work shows that it is possible to use blood tests, which are much less expensive and more accessible than brain scans or spinal fluid tests, to predict the onset of Alzheimer’s symptoms,” said lead author Suzanne E. Schindler, MD, PhD, associate professor in the WashU Medicine Department of Neurology. She explained that these models could shorten the time needed to evaluate potential preventive therapies.

“In the short term, these models will accelerate our research and clinical trials,” she said. “Ultimately, the goal is to be able to tell individual patients when they are likely to develop symptoms, which will help them and their doctors develop a plan to prevent or slow down the symptoms.”

The Role of the Blood Biomarker p tau217

The research was conducted as part of a project organized by the Foundation for the National Institutes of Health Biomarkers Consortium, a public-private partnership that includes WashU Medicine.

The predictive approach focuses on measuring p tau217, a protein found in plasma, the liquid component of blood. By analyzing the concentration of this protein, the researchers estimated the age at which a person might develop Alzheimer’s symptoms. Today, p tau217 tests can help doctors diagnose Alzheimer’s in patients who are already experiencing cognitive impairment. However, these tests are not recommended for people without symptoms outside of research studies or clinical trials.

To better understand how long it typically takes for symptoms to appear after an increase in p-tau217 levels, Schindler and lead author Kellen K. Petersen, PhD, assistant professor of neurology at WashU Medicine, examined data from 603 older adults living independently. The participants were enrolled in two long-term studies: the WashU Medicine Knight Alzheimer Disease Research Center (Knight ADRC) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI), which involves multiple research sites across the US.

Tests on Multiple Platforms

In the Knight ADRC group, plasma p-Tau217 was measured using PrecivityAD2, a clinically available Alzheimer’s blood test developed by C2N Diagnostics. C2N is a Washington University start-up company founded by researchers David M. Holtzman, MD, Barbara Burton and Reuben M. Morriss III Distinguished Professor, and Randall J. Bateman, MD, Charles F. & Joanne Knight Distinguished Professor of Neurology. Both are co-authors of the study. In the ADNI cohort, p-tau217 levels were measured using tests from other companies, including one approved by the US Food and Drug Administration.

Previous research has shown that p-tau217 in plasma accurately reflects the accumulation of amyloid and tau in the brain, as seen on PET scans. Amyloid and tau are abnormal proteins that gradually accumulate and are considered hallmarks of Alzheimer’s disease. They can accumulate many years before memory problems appear.

“Amyloid and tau levels are like tree rings—if we know how many rings a tree has, we know how old it is,” Petersen said. “It turns out that amyloid and tau also accumulate in a consistent pattern, and that the age at which they become positive strongly predicts when someone will develop Alzheimer’s symptoms. We found that this is also true for plasma p-tau217, which reflects both amyloid and tau levels.”

Predicting the Timing of Symptoms Within a Few Years

The researchers found that their model could estimate the age at which symptoms would appear with an accuracy of about three to four years. Age also influenced how quickly symptoms followed rising p-tau217 levels. Older adults tended to develop symptoms earlier after the protein was elevated than younger people. This pattern suggests that younger brains can tolerate disease-related changes for longer, while older adults may show symptoms even at lower levels of the underlying pathology.

For example, a person whose p-tau217 levels rose at age 60 developed symptoms about 20 years later. In contrast, symptoms typically appeared about 11 years later when levels first rose at age 80. The model also performed well on other p-tau217-based diagnostic tests besides PrecivityAD2, underscoring its reliability and broader applicability.

To encourage further research, the team made the code for model development publicly available. Petersen also developed a web-based application that allows researchers to explore the clock models in more detail. “These clock models could make clinical trials more efficient by identifying individuals who are likely to develop symptoms within a certain period of time,” Petersen said. “With further refinements, these methods have the potential to predict symptom onset with such accuracy that we could use them in individualized clinical care.” He added that other blood biomarkers are associated with cognitive decline in Alzheimer’s disease and that combining additional markers in future studies could further improve predictions of symptom onset.