A blood-based measure of phosphorylated tau217 can estimate when individuals are likely to develop symptomatic Alzheimer’s disease, potentially years before memory problems begin.
In a study published in Nature Medicine, investigators developed and validated statistical models that use longitudinal plasma p-tau217 levels to predict the timing of cognitive symptom onset. Rather than serving only as a binary marker of disease presence, p-tau217 was incorporated into “disease clocks” designed to estimate proximity to clinical conversion.
Clock models based on amyloid and tau positron emission tomography (PET) have already shown promise in predicting the onset of Alzheimer's symptoms. However, due to the limited availability of PET testing, a plasma-based model would improve accessibility.
P-tau217 reflects abnormal tau accumulation, a core feature of Alzheimer’s pathology. In plasma, p-tau217 levels are observed to rise progressively during the preclinical phase and accelerate as individuals approach symptom onset. By modeling these trajectories, the researchers were able to estimate an individual’s time to symptomatic disease with clinically meaningful precision across independent cohorts.
The study demonstrates that p-tau217 clocks retained predictive performance across diverse study populations and were associated with established imaging and cerebrospinal fluid markers of Alzheimer’s pathology.
Researcher Suzanne Schindler, from WashU Medicine Department of Neurology, said, “Our work shows the feasibility of using blood tests, which are substantially cheaper and more accessible than brain imaging scans or spinal fluid tests, for predicting the onset of Alzheimer’s symptoms.”
“In the near term, these models will accelerate our research and clinical trials,” Schindler added. “Eventually, the goal is to be able to tell individual patients when they are likely to develop symptoms, which will help them and their doctors to develop a plan to prevent or slow symptoms.”
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