Columbia University researchers report elevated plasma p-tau217 combined with APOE4 genetic testing predicts cognitive symptom onset within three to four years in asymptomatic individuals.
Combining a blood test measuring phosphorylated-tau 217 (p-tau217) with genetic testing for the APOE4 variant can forecast when high-risk individuals will develop their first symptoms of Alzheimer’s disease, according to a study led by Columbia University researchers and published in The Lancet Neurology.
The study analyzed data from approximately 8,500 participants across diverse ethnic backgrounds to assess whether biomarker and genetic profiling could predict symptom onset in currently asymptomatic individuals, according to a Columbia University Irving Medical Center release. The investigators found that once plasma p-tau217 levels become elevated, individuals carrying one or more copies of the APOE4 gene typically develop symptoms within three to four years, whereas those with other APOE variants develop symptoms within five to six years.
“The combination of the tests really makes a difference in predictive power. And the projections are the same for everyone regardless of their background,” says Richard Mayeux, MD, chair of the department of neurology at Columbia University Vagelos College of Physicians and Surgeons and neurologist-in-chief at NewYork-Presbyterian/Columbia University Irving Medical Center, in a release. “What this will allow us to do is make better predictions about the onset of symptoms in people at risk, and when preventative drugs become available, prescribe those at the right time.”
Improving Predictive Power Beyond Biomarkers Alone
Assays measuring p-tau217, a plasma biomarker reflecting amyloid and tau pathology in the brain, have become increasingly common in clinical settings to confirm or rule out Alzheimer’s disease in older adults experiencing cognitive decline or memory loss, according to the release. Although elevated p-tau217 can be detected in asymptomatic patients, predictions of symptom timing based on the biomarker alone have lacked sufficient precision for clinical prognostic utility.
To improve prognostic accuracy, the investigators evaluated the addition of testing for APOE4, which represents the strongest known genetic risk factor for Alzheimer’s disease and is present in approximately one in five individuals, according to the study release.
Clinical Implications for Asymptomatic Testing and Trials
Despite the predictive capacity of the dual-testing strategy, the authors caution that routine clinical testing of asymptomatic individuals is not recommended under current treatment protocols. “I don’t recommend that people get these tests right now if they’re asymptomatic,” says Mayeux in a release. “What would you do with that information?”
Currently approved monoclonal antibody therapies for Alzheimer’s disease are indicated only for symptomatic patients, leaving asymptomatic individuals ineligible for treatment, according to the release. However, an active clinical trial is evaluating whether monoclonal antibodies can slow disease progression when administered to asymptomatic patients who present with elevated p-tau217 levels, alongside multiple other disease-modifying therapies currently in development.
“If you have a drug that could prevent disease, what would be the optimal time to give it to people? Our data is telling us, for people at high risk with APOE4 genes, the best time is when their ptau levels elevate, about three years before symptoms emerge,” says Mayeux in a release.
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