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Biomarkers.

Peter R Millar1, Stephanie Doering2, Babatunde Adeyemo3

  • 1Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 24, 2025
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Summary
This summary is machine-generated.

Researchers identified three distinct Alzheimer's disease (AD) tau PET subtypes, showing unique patterns in amyloid-beta (Aβ) deposition and brain connectivity. These findings may explain differences in tau spreading in AD.

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Area of Science:

  • Neuroimaging
  • Alzheimer's Disease Research
  • Biomarker Discovery

Background:

  • Spatiotemporal tau accumulation patterns vary across Alzheimer's disease (AD) phenotypes.
  • Tau PET imaging can identify these patterns, potentially influenced by amyloid-beta (Aβ) deposition and network connectivity (RSFC).

Purpose of the Study:

  • To replicate tau PET subtypes using the SuStaIn model.
  • To investigate subtype-specific differences in Aβ PET deposition and RSFC patterns.

Main Methods:

  • Utilized the Subtype and Stage Inference (SuStaIn) model on 820 tau PET scans from 629 participants.
  • Analyzed resting-state functional connectivity (RSFC) and amyloid-beta (Aβ) PET (PiB or FBP) data.
  • Harmonized Aβ PET data to Centiloid for standardized comparison.

Main Results:

  • Identified three tau PET subtypes: limbic predominant, posterior predominant, and MTL-sparing.
  • MTL-sparing subtype showed younger age, greater impairment, and higher Aβ PET levels.
  • Posterior predominant subtype exhibited distinct RSFC patterns and lower Aβ PET in some regions compared to limbic predominant.

Conclusions:

  • Replicated three distinct tau PET subtypes in an independent AD cohort.
  • Observed novel differences in Aβ PET and RSFC spatial patterns specific to each subtype.
  • These subtype-specific network and deposition patterns may influence tau spreading in AD.