According to results of a study published in JAMA Neurology, plasma phosphorylated tau 217 (p-tau217) levels were associated with amyloid β (Aβ) status in individuals with preclinical Alzheimer disease (AD), which highlights the potential application of p-tau217 tests for participant selection in preclinical AD trials as well as patient eligibility for disease-modifying therapies.

Researchers analyzed data from 2916 cognitively unimpaired individuals (June 2009–March 2024) across the United States, Europe, Australia, and Canada with available plasma p-tau217 levels and who were Aβ positive as determined by PET or cerebrospinal fluid (CSF) test. Researchers also performed a comparison between mass spectrometry and immunoassay-based p-tau217 measurements (n=964).

  • Stand-alone plasma p-tau217 testing identified Aβ positivity with a positive predictive value of 79% (95% CI, 74 to 84) and an overall accuracy of 81% (95% CI, 80 to 82).
  • A sequential two-step workflow (plasma screen followed by confirmatory PET or CSF test) was associated with higher diagnostic performance, achieving a PPV of 91% (95% CI, 86 to 95) and improved overall accuracy.
  • Immunoassay-based p-tau217 measurement yielded a PPV comparable to mass spectrometry (80% [95% CI, 74 to 86] vs 85% [95% CI, 81 to 90]; P=.12), but were associated with lower overall accuracy (82% [95% CI, 79 to 84] vs 88% [95% CI, 86 to 90]; P<.001) and a lower true Aβ-positive detection rate (49% [95% CI, 43 to 55] vs 69% [95% CI, 64 to 75]; P<.001).

Researchers note that plasma p-tau217 tests offer a scalable, lower-burden, and cost-effective frontline screening method to identify individuals with preclinical AD for cases in which a moderate accuracy of Aβ status is required or as part of a 2-step pathway alongside confirmatory PET or CSF testing for cases in which high accuracy of Aβ status is required. In addition, incorporating plasma p-tau217 tests into tailored workflows may streamline participant selection for preclinical trials and help inform clinical decisions about eligibility for disease-modifying therapies.

Source: Salvadó G, Janelidze S, Bali D, et al. Plasma phosphorylated tau 217 to identify preclinical Alzheimer disease. JAMA Neurol. Published online September 15, 2025. doi:10.1001/jamaneurol.2025.3217