Plasma p-tau217 provides long-term prognostic information for individuals with no cognitive impairment at baseline.A pooled analysis presented at AAIC® 2026 demonstrated a consistent association between higher levels of plasma phosphorylated tau 217 (p-tau217) and an increased risk of clinical progression and accelerated cognitive decline in a large cohort of older adults without cognitive impairment.
“Our [study provides] some of the clearest evidence yet that elevated p-tau217 levels may help detect dementia risk years earlier, even in adults with no noticeable memory or thinking problems,” noted lead author Dr Rachel Buckley from Harvard Medical School, Boston, Massachusetts, US, in the AAIC 2026 press release.
Every 1-SD increase in baseline p-tau217 level correlated with an increased risk of progression to cognitive impairment (hazard ratio [HR], 1.38; p<0.001). This association remained significant after adjusting for covariates, including β-amyloid PET scan Centiloids (HR, 1.32). [AAIC 2026, abstract 9890]
The 2-year absolute risk of incident cognitive impairment was very low irrespective of p-tau217 category (1–4 percent). For the 5-year horizon, the absolute risks were 12, 15, 24, and 38 percent in the respective low (less than –0.5 SD), intermediate (–0.5 to <1.1 SD), high (1.1 to <2.5 SD), and very high (≥2.5 SD) p-tau217 categories.
The absolute risks over 10 years were markedly higher than those observed at 5 years (40, 45, 62, and 78 percent for the low, intermediate, high, and very high categories, respectively). However, the researchers noted that the 10-year absolute risk estimates should be interpreted with caution due to limited data.
In the published manuscript, Buckley and colleagues specified that the longer time horizon may be particularly relevant for individuals with high—but not very high—baseline p-tau217 levels, as they are included in the current prevention trials. “[Despite their potentially] lower imminent risk of decline, they may have substantial risk of impairment over a decade.” [JAMA 2026:e2612556]
“[The findings are] most immediately relevant to risk stratification for research and clinical trial enrichment and are not yet precise enough to guide individualized prognosis, which is necessary for clinical care. Current clinical practice guidelines explicitly recommend against p-tau217 testing in cognitively unimpaired individuals,” the investigators added.
Prognostic significance
This study used harmonized data from 2,684 older adults without cognitive impairment (median age 69.6 years, 63 percent women) across six major Alzheimer’s trials. A majority of the participants had intermediate p-tau217 levels (n=1,087), while 598 had high, 516 had low, and 483 had very high levels.
A total of 478 events of progression to cognitive impairment were reported over a median follow-up of 5.4 years.
“In this longitudinal study of several select cohorts, plasma p-tau217 provided long-term prognostic information for individuals with no cognitive impairment at baseline, laying the groundwork for possible future development of individualized risk prediction scores,” said Buckley and colleagues.
“By providing absolute risk estimates of progression to cognitive impairment, this [study] moves the field closer to presymptomatic risk stratification with p-tau217, supporting trial design. Further validation in population-representative epidemiological cohorts will be required before p-tau217–based estimates can inform individual clinical prognosis and clinical decision-making,” they concluded.
In the press release, Alzheimer’s Association chief science officer and medical affairs lead Dr Maria Carrillo commented, “This is the future of Alzheimer’s care, targeting the earliest stages of the disease, including in its silent stage before memory issues arise. This is when treatments may have the greatest benefit, perhaps even keeping people from ever experiencing dementia symptoms.”
“Identifying people at risk earlier could fundamentally change how we diagnose, treat, and prevent dementia, with far-reaching health, happiness, and cost implications for patients, families, healthcare systems, and society,” Carrillo added.