HAI Book 2025 - Flipbook - Page 355
McVea, Andrew
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APOE4 associated with higher off-target meninges signal with [F18]MK6240 PET
Andrew McVea1, Alexandra DiFilippo1, Max McLachlan1, Brecca Bettcher1, Dana Tudorascu2,
Sterling Johnson1, Matthew Zammit1, Tobey Betthauser1, Bradley Christian1
1
University of Wisconsin - Madison, Madison, WI, US
University of Pittsburgh, Pittsburgh, PA, US
2
Background: Individuals with the APOE4 allele have an enhanced risk of Alzheimer9s disease (AD) and APOE4
carriage is associated with earlier onset of AD pathology including tau aggregation. [F-18]MK6240 is a PET
radioligand that binds to tau aggregates in AD with variable off-target signal surrounding the cortex in the
meninges that can influence quantification. Previous studies examining MK6240 signal have shown significantly
higher meninges uptake in females and PET signal dependence on scanner model. The goal of this investigation is
to evaluate meninges MK6240 signal in a large cohort to study the relationship between APOE4 carriage and
meninges uptake.
Method: Participants were scanned at the University of Wisconsin3Madison on a Biograph Horizon mCT or ECAT
HR+ (Table 1). MK6240 PET images were smoothed using a 6mm3 gaussian kernel then processed using a
standardized pipeline to generate SUVR images using the inferior cerebellar grey matter reference region. A
meninges ROI was created by diluting the MNI-152 cortical brain mask by 5mm and then subtracting the original
mask (Fig. 1). Statistical comparisons were made using a multiple regression model examining the association
between meninges SUVR and APOE4 carriage with sex, scanner model and the interaction terms between
variables as covariates.
Results: Higher average meninges signal was observed for APOE4 carriers (p = 0.03), and similar to previous
results, for females (p < 0.001) and participants imaged on the mCT (p < 0.001). The interaction term between
scanner and sex was significant (p = 0.02), while interactions between sex and APOE status (p = 0.34) and scanner
and APOE4 carriage were non-significant (p = 0.42).
Conclusions: Meninges signal is a highly variable factor in MK6240 imaging that can bias tracer uptake outcomes.
The relationships between APOE4 carriage and sex on meninges uptake should be accounted for in MK6240
quantification and population-based comparisons.
HAI2025 - 355
