HAI Book 2025 - Flipbook - Page 216
Guzmán, Diana S
46
Regional amyloid and tau: Exploring regional sex-based differences
in a middle-aged community-based cohort
Diana S Guzmán1, Froogh Aziz1, Anna C Smith1, Hannah Houlihan1, Thairi C Sanchez1, José A
Luchsinger1, Patrick J Lao1
1
Columbia University Medical Center, New York, NY, US
Background: As previously reported in the Northern Manhattan Study of Metabolism and Mind (NOMEM) study,
women have greater global amyloid and tau burden, yet less neurodegeneration in AD signature regions compared
to men. We sought to characterize regional sex differences in amyloid and tau burden in this middle-aged
community-based cohort.
Methods: 541 NOMEM participants underwent Florbetaben PET and 391 NOMEM participants underwent MK-6240
PET (Table 1). Florbetaben SUVR was assessed in Thal phase regions (parietal cortex, frontal cortex, temporal
cortex, cingulate gyrus, and striatum) and MK-6240 SUVR in Braak stage regions (I-VI). ROI-level and voxelwise sex
differences were adjusted for age, APOE4, and for global amyloid in tau models.
Results: On the ROI-level, women had greater amyloid across Thal phase regions and greater tau across all Braak
stage regions without much regional variability. On the voxel-level, women had greater amyloid in Thal phase
regions and the occipital cortex. Women had greater tau in Braak stage regions, with a right sided laterality in the
temporal cortex. Non-brain uptake in the leptomeninges, scalp, and ventricles was greater in women for
Florbetaben and MK-6240.
Conclusion: Women had greater amyloid burden diffusely across the brain, extending to the occipital cortex, and
greater tau burden in the right temporal cortex. Cerebral amyloid angiopathy and verbal memory should be further
explored in relation to occipital cortex involvement from amyloid and relative sparing of the left temporal cortex
from tau in women. Differential partial volume effect (i.e., men had lower cortical thickness and greater
ventricular volume) or off-target binding profiles should also be considered when assessing sex differences.
HAI2025 - 216
