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Subtracting First Principal Component May Improve 4R Tau Detectability on [18F]Flortaucipir Tau PET.

Ryota Satoh1, Farwa Ali2, Dennis W Dickson3

  • 1Department of Radiology, Mayo Clinic, Rochester, Minnesota; satoh.ryota@mayo.edu.

Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine
|January 22, 2026
PubMed
Summary

Subtracting a principal component from [18F]flortaucipir PET scans improves detection of four-repeat (4R) tau in progressive supranuclear palsy (PSP). This method enhances diagnostic performance for 4R tauopathies, offering new potential for imaging these conditions.

Keywords:
4R tauPSP[18F]flortaucipirprincipal component analysis

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Area of Science:

  • Neuroimaging
  • Molecular Imaging
  • Neuropathology

Background:

  • [18F]flortaucipir PET shows limited sensitivity for detecting four-repeat (4R) tau pathology, hindering its use in 4R tauopathies like progressive supranuclear palsy (PSP).
  • Principal component analysis (PCA) has been suggested to isolate non-disease-related tau uptake in non-Alzheimer tauopathies, potentially obscuring 4R tau signals.

Purpose of the Study:

  • To test if subtracting the first principal component (PC1) from [18F]flortaucipir PET images can enhance sensitivity to 4R tau in a large cohort of PSP patients.
  • To evaluate the impact of PC1 subtraction on the diagnostic performance of [18F]flortaucipir PET in differentiating PSP from controls and across PSP clinical variants.

Main Methods:

  • Prospectively recruited PSP patients (n=141) and controls (n=102) underwent [18F]flortaucipir PET scans.
  • The first principal component (PC1) was extracted from control SUVR images and subtracted from remaining controls and all PSP patients.
  • Diagnostic performance was compared before and after PC1 subtraction using receiver operating characteristic (ROC) curves, analysis of SUVR differences, and correlation with tau pathology severity.

Main Results:

  • PC1 subtraction significantly improved the area under the ROC curve for differentiating PSP from controls in frontal white matter (0.54 to 0.67) and subcortical regions (0.69 to 0.87).
  • After PC1 subtraction, the PSP-cortical variant showed higher SUVR than other PSP variants in frontal regions, and correlations between SUVR and tau pathology severity were observed in more regions (precentral gyrus, superior frontal gyrus, red nucleus).

Conclusions:

  • Subtracting the first principal component from [18F]flortaucipir PET data enhances diagnostic performance in PSP.
  • This method improves sensitivity to 4R tau, suggesting its utility for detecting subtle tau uptake in non-Alzheimer tauopathies like PSP.