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Clinical Manifestations.

Bruna Bellaver1, Guilherme Povala1, Pamela C L Ferreira1

  • 1University of Pittsburgh, Pittsburgh, PA, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 26, 2025
PubMed
Summary
This summary is machine-generated.

MK6240 tau PET abnormalities emerge earlier than plasma p-tau217 and Flortaucipir with increasing amyloid-beta burden. Discordant results between tau PET and plasma p-tau217 suggest varied biomarker emergence, with potential clinical relevance.

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Area of Science:

  • Neuroimaging
  • Biomarkers
  • Alzheimer's Disease Research

Background:

  • Distinct tau PET tracer binding characteristics influence biomarker trajectories in Alzheimer's disease (AD).
  • Investigating the relationship between tau PET tracers (MK6240, Flortaucipir) and plasma p-tau217 abnormalities relative to amyloid-beta (Aβ) PET deposition.
  • Assessing concordance between tau PET, plasma p-tau217, and cognitive performance.

Purpose of the Study:

  • To compare the emergence of MK6240 and Flortaucipir tau PET positivity with plasma p-tau217 abnormalities.
  • To evaluate the concordance between tau PET and plasma p-tau217 positivity across the AD continuum.
  • To examine the relationship between discordant biomarker profiles and cognitive function.

Main Methods:

  • Analysis of 352 participants (HEAD study) with Aβ PET, tau PET (MK6240, Flortaucipir), and plasma biomarkers (p-tau217, GFAP).
  • Modeling tau PET and plasma p-tau217 trajectories as a function of Aβ burden (Centiloid) using Lowess.
  • Defining biomarker positivity based on z-scores anchored on young individuals (≥2.5 z-score).

Main Results:

  • MK6240 showed abnormality earliest (22 Centiloids), followed by plasma p-tau217 (38 Centiloids), and Flortaucipir (56 Centiloids).
  • High concordance (∼80%) observed between tau PET and plasma p-tau217 positivity.
  • Discordant cases (e.g., MK6240+/p-tau217- or MK6240-/p-tau217+) exhibited distinct Aβ burden and cognitive profiles.

Conclusions:

  • MK6240 detects abnormalities at lower Aβ burden compared to plasma p-tau217 and Flortaucipir.
  • Significant discordance between tau PET and plasma p-tau217 suggests varied individual biomarker emergence patterns.
  • Distinct cognitive profiles in discordant groups highlight potential clinical significance requiring further research.