Blood Test May Predict Alzheimer’s Symptoms Up to a Decade Early

Very high levels of plasma phosphorylated tau 217 (p-tau217), a marker of amyloid burden in the brain, predicted future risk of cognitive impairment among older adults who were initially unimpaired, a multicohort study suggested.

Using different plasma assays and definitions of cognitive impairment across six cohorts, a “consistent pattern” emerged: those with very high p-tau217 had an estimated 38% risk of cognitive impairment over 5 years and an estimated 78% risk over 10 years, reported Rachel Buckley, PhD, of Mass General Brigham in Boston, at the Alzheimer’s Association International Conference. The findings were published simultaneously in JAMA.

P-tau217 provided predictive information beyond amyloid PET, suggesting it may capture aspects of Alzheimer’s disease biology not explained by amyloid plaques alone, Buckley said.

Elevated p-tau217 was associated with faster cognitive decline in latent Preclinical Alzheimer Cognitive Composite (PACC) scores, she noted. The 5-year annualized decline for the very high p-tau217 group was -0.07 latent PACC units/year, compared with 0.03 units/year in the low p-tau217 group.

“These findings should not yet be interpreted as support for routine screening in asymptomatic individuals as plasma p-tau217 is not recommended for testing in cognitively unimpaired older adults,” Buckley said.

“Rather, they move us toward individualized p-tau217-based risk estimates for future cognitive impairment over clinically meaningful time frames, which will be critical as prevention strategies hopefully become a reality in the near future,” she told MedPage Today.

Alzheimer’s disease is the most common cause of dementia in older individuals, noted Suzanne Schindler, MD, PhD, of Washington University School of Medicine in St. Louis, and David Wolk, MD, of the University of Pennsylvania in Philadelphia, in an accompanying editorial.

With the approvals of the disease-modifying, amyloid-targeting therapies lecanemab (Leqembi) and donanemab (Kisunla), incorporating Alzheimer’s biomarkers into clinical practice has become more important for medical decision-making, Schindler and Wolk observed.

“Among the blood-based biomarkers, plasma phosphorylated tau 217 has demonstrated the highest accuracy in detecting amyloid pathology and also reflects tau pathology to some degree,” they wrote.

Clinical practice guidelines limit testing for Alzheimer’s pathology to individuals with objective cognitive impairment who are undergoing diagnostic evaluation in specialty care, Schindler and Wolk pointed out.

“However, in the research setting, unimpaired individuals with biomarker evidence of Alzheimer’s disease pathology have been the focus of numerous natural history studies and, more recently, secondary prevention trials testing whether targeting pathology can forestall the onset of cognitive impairment,” they noted.

Buckley and colleagues pooled data from 2,684 cognitively unimpaired older adults in six observational study and clinical trial cohorts in North America, Japan, and Australia. Blood samples were tested for p-tau217 levels and PET imaging was conducted at enrollment. The earliest enrollment was in 2004 and the most recent follow-up was in 2025.

The primary outcome was time to progression to cognitive impairment, based on global Clinical Dementia Rating scores. Over a median follow-up of 5.4 years, 478 participants progressed to cognitive impairment. Only 5% of participants were followed for more than 10 years.

The study has some caveats, Buckley acknowledged. “The findings are based on data from study participants who are generally higher in education and lower in geographic and racial diversity, and so we continue to gather more data from epidemiological and real-world settings that will help us to refine our estimates even more,” she said.

“While we provide some of the first 10-year estimates of risk for cognitive impairment, there is less data available up at that end,” she added. “We will need to continue following these participants over time to make sure our estimates are stable.”