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Biomarkers.

Andrew K McVea1, Max McLachlan2, Brecca Bettcher2

  • 1University of Wisconsin - Madison, Madison, WI, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 25, 2025
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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 status and sex is crucial for accurate quantification and comparisons.

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Area of Science:

  • Neuroimaging
  • Alzheimer's Disease Research
  • Radioligand Development

Background:

  • APOE4 allele increases Alzheimer's disease (AD) risk and tau pathology onset.
  • [F-18]MK6240 PET ligand binds tau aggregates but can have off-target meningeal signal.
  • Previous studies noted higher meninges signal in females and scanner dependency.

Purpose of the Study:

  • To compare meninges [F-18]MK6240 signal between APOE4 carriers and non-carriers.
  • To investigate the influence of APOE4 carriage on PET tracer quantification.
  • To assess factors affecting off-target radioligand accumulation.

Main Methods:

  • 1051 participants scanned on Biograph Horizon mCT or ECAT HR+ scanners.
  • Standardized PET image processing to generate SUVR images with cerebellar reference region.
  • Multiple regression analysis comparing meninges SUVR for APOE4 carriers vs. non-carriers, including sex and scanner as covariates.

Main Results:

  • Higher average meninges signal observed in APOE4 carriers (p=0.03) and females (p<0.001).
  • Participants scanned on the mCT scanner showed higher meninges signal (p<0.001).
  • Sensitivity analysis revealed higher signal in female APOE4 carriers on the HR+ (p=0.009) and mCT (p=0.05).

Conclusions:

  • Meninges [F-18]MK6240 signal variability can bias PET quantification in AD studies.
  • APOE4 carriage and sex significantly influence meninges signal.
  • These factors must be considered for accurate [F-18]MK6240 quantification and population comparisons in AD research.