Researchers from Washington University School of Medicine in St. Louis have developed a groundbreaking method that predicts when an individual is likely to exhibit symptoms of Alzheimer’s disease through a single blood test. This advancement, published on February 19 in Nature Medicine, offers the potential to identify Alzheimer’s symptoms up to three to four years in advance, which could significantly influence clinical trials for preventive treatments and help pinpoint individuals who would most benefit from these interventions.
Over 7 million Americans currently live with Alzheimer’s, and the costs associated with healthcare and long-term care for those affected by Alzheimer’s and other dementias are projected to reach nearly $400 billion by 2025, according to the Alzheimer’s Association. While there is currently no cure for this significant public health challenge, predictive models could facilitate the development of treatments aimed at delaying or preventing the onset of Alzheimer’s symptoms.
“Our work demonstrates the feasibility of using blood tests that are substantially more cost-effective and accessible than brain imaging or cerebrospinal fluid analysis to predict the onset of Alzheimer’s symptoms,”
Suzanne E. Schindler, MD, PhD, Lead Author, Associate Professor of Neurology at WashU Medicine
Dr. Schindler noted that these models could expedite clinical studies focused on potential preventive treatments. “In the short term, these models will accelerate our research and clinical trials,” she stated. “Ultimately, the goal is to inform individual patients when they are likely to develop symptoms, assisting them and their healthcare providers in planning prevention or management strategies.”
Protein to Predict Symptom Onset
This study forms part of a larger initiative led by the Foundation for the National Institutes of Health Biomarkers Consortium, which represents a public-private partnership that includes WashU Medicine. The predictive models developed by Dr. Schindler and her team leverage a protein known as p-tau217 found in a person’s plasma—the liquid component of blood—to estimate the age at which they may begin exhibiting symptoms of the neurodegenerative disorder. Currently, p-tau217 levels in plasma are utilized to aid in diagnosing Alzheimer’s in patients exhibiting cognitive impairments; however, these tests are not recommended for cognitively unimpaired individuals outside of clinical trials or research settings.
To assess the timeline connecting elevated p-tau217 levels and Alzheimer’s symptoms, the researchers analyzed data from volunteers participating in two independent, long-term Alzheimer’s research initiatives: the WashU Medicine Knight Alzheimer Disease Research Center (Knight ADRC) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI) across multiple U.S. sites. The study included 603 older adults living independently in the community.
Plasma p-tau217 was measured using PrecivityAD2, a clinically available diagnostic blood test for Alzheimer’s developed by C2N Diagnostics, a start-up founded by WashU Medicine researchers. This measurement was also validated in the ADNI cohort using blood tests from various companies, including one approved by the U.S. Food and Drug Administration.
Data from PET scans have demonstrated a strong correlation between plasma p-tau217 levels and the accumulation of amyloid and tau proteins in the brain, which are characteristic features of Alzheimer’s disease. These misfolded proteins typically accumulate years before any symptoms appear.
“Amyloid and tau levels are akin to the rings of a tree—just as we can determine a tree’s age by counting its rings, we can infer the timing of the accumulation of these proteins to predict when someone will develop Alzheimer’s symptoms,” said Dr. Petersen, the study’s lead author and instructor of neurology at WashU Medicine. “We discovered that the same pattern holds true for plasma p-tau217, which mirrors both amyloid and tau levels.”
The predictive models estimate the onset of symptoms within a margin of error of three to four years. The researchers found that older adults generally experience symptoms sooner compared to younger participants, indicating that the brains of younger individuals may be more resilient to neurodegeneration. For instance, if a person at age 60 has elevated p-tau217 levels, they may exhibit symptoms 20 years later. In contrast, if these levels were elevated at 80, symptoms might only develop 11 years later.
The team highlighted that their predictive model performed consistently across different p-tau217-based diagnostic tests, underscoring the robustness and generalizability of their approach. They made the full code for model development available to assist other researchers in further refining the models and created a web-based application enabling detailed exploration of the predictive models.
“These predictive models could enhance the efficiency of clinical trials by identifying individuals likely to present symptoms within a specified timeframe,” said Dr. Petersen. “With additional refinement, these methodologies could predict symptom onset with such accuracy that they could be implemented in individual clinical care.” The authors also noted that further blood biomarkers associated with cognitive symptoms of Alzheimer’s may be used to refine onset estimates in future research endeavors.
