Neurology · 2 h ago
Plasma p-tau217 and amyloid PET discordance linked to distinct biomarker profiles
A study of 1,069 cognitively normal adults in two cohorts examined biomarker and clinical differences across plasma p-tau217 and amyloid PET result patterns. Discordant results were associated with distinct profiles, and p-tau217 positivity was linked to greater clinical progression risk in longitudinal analyses; the authors say operating thresholds need validation before clinical use.
- Discordant test patterns showed distinct biomarker profiles.
- Both p-tau217-positive groups had higher progression risk in ADNI.
- Threshold choice affected observed amyloid accumulation.
- Authors call for validation before clinical use.
Researchers analyzed cognitively normal participants in the Chinese Preclinical Alzheimer’s Disease Study (CPAS; n=594) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI; n=475). Amyloid PET positivity was defined as a Centiloid value of at least 20. Cohort-specific p-tau217 cutoffs were anchored to PET results and set at a specificity of at least 90%, classifying participants into four p-tau/PET groups. The analyses compared biomarkers and cognition at baseline and assessed longitudinal outcomes in ADNI.
Compared with participants negative on both tests, those who were p-tau217-positive but PET-negative had higher GFAP and neurofilament light chain levels in both cohorts. The p-tau217-negative/PET-positive group had a lower plasma Aβ42/40 ratio in ADNI, while participants positive on both tests showed the broadest biomarker abnormalities. In ADNI, both p-tau217-positive groups had higher clinical progression risk and faster decline in selected cognitive domains; both PET-positive groups had faster Centiloid accumulation. Faster accumulation in the p-tau217-positive/PET-negative group appeared only at lower specificity thresholds.
The findings suggest that discordant results may carry different biological and prognostic information, depending on the direction of discordance and the p-tau217 cutoff. The study is observational, and its results do not establish clinical utility. The authors say different operating thresholds may help risk enrichment or prioritization for confirmatory testing, but require validation before clinical use.
In practice
For cognitively normal adults undergoing preclinical Alzheimer’s biomarker assessment, a plasma p-tau217 result that conflicts with amyloid PET should not be interpreted as a single uniform category: the direction of discordance and the p-tau217 cutoff were associated with different biomarker profiles, and p-tau217-positive groups had higher progression risk in ADNI. These observational findings may inform research risk stratification, but the authors state that operating points require validation before clinical use; they do not establish a basis for changing care.
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Alzheimer's & Dementia: Direction‐specific biomarker profiles and clinical significance of plasma p‐tau217/amyloid PET discordance in cognitively normal adults ↗This is an automated AI-condensed summary that has not yet been reviewed by an editor. Always consult the full item at the original source.