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Summary
This summary is machine-generated.

APOE4 carriers and females show higher [F-18]MK6240 meninges signal, impacting Alzheimer's disease PET imaging. Accounting for APOE4 carriage and sex is crucial for accurate MK6240 quantification and comparisons.

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Area of Science:

  • Neuroimaging
  • Alzheimer's Disease Research
  • Radioligand Development

Background:

  • Individuals with the APOE4 allele have an increased lifetime risk for Alzheimer's disease (AD), including earlier onset of amyloid and tau pathology.
  • [F-18]MK6240 is a PET radioligand for imaging tau aggregates in AD, but off-target meningeal signal can affect quantification.
  • Previous studies noted higher meningeal [F-18]MK6240 signal in females and dependence on scanner models.

Purpose of the Study:

  • To compare meningeal [F-18]MK6240 signal magnitude and distribution between APOE4 carriers and non-carriers.
  • To investigate the influence of APOE4 carriage on tau PET imaging.
  • To assess potential biases in Alzheimer's disease PET quantification.

Main Methods:

  • 1051 participants were scanned using PET on Biograph Horizon mCT or ECAT HR+ scanners.
  • Standardized pipeline generated SUVR images, with a 5mm diluted cortical mask used for meninges ROI analysis.
  • Multiple regression compared meningeal SUVR between APOE4 carriers and non-carriers, including sex and scanner model as covariates.

Main Results:

  • Higher average meningeal [F-18]MK6240 signal was observed in APOE4 carriers (p=0.03), females (p<0.001), and on the mCT scanner (p<0.001).
  • No significant interaction terms were found between variables.
  • Sensitivity analysis in females revealed significantly higher meningeal signal in APOE4 carriers on the HR+ (p=0.009) and mCT (p=0.05).

Conclusions:

  • Meningeal [F-18]MK6240 signal variability can bias tau PET outcomes in Alzheimer's disease studies.
  • APOE4 carriage and sex are significant factors influencing meningeal signal.
  • These relationships must be considered for accurate MK6240 quantification and population comparisons in AD research.