Extended Data Fig. 5: Amyloid and tau PET analysis in APOE4 carriers and correction of ¹⁸F-AV1451 off-target binding in the choroid plexus.

All studies were performed in individuals with CDR score 0. Amyloid and tau PET studies were conducted using ¹⁸F- FBB or ¹⁸F- FBP, and ¹⁸F- AV1451, respectively. For amyloid PET data analysis, FBP and FBB data sets were combined. a, Uptake of amyloid tracers by the OFC in APOE4 (n = 29) relative to APOE3 (n = 45) carriers (voxel-wise two-sample one-tailed t-tests). b, Representative amyloid PET SUVR maps from an APOE3 homozygote (top) and an APOE4 carrier (APOE4) (bottom). Slices 1 and 2, regions of interest (ROIs) for amyloid PET and BBB DCE-MRI scans (see e). Arrow, amyloid tracer uptake by OFC. The APOE3 and APOE4 representative images used FBP. c, Uptake of tau tracer shows undetectable tau accumulation in APOE3 (n = 60) or APOE4 (n = 37) carriers (voxel-wise two-sample one-tailed t-tests). d, Representative tau PET SUVR maps from APOE3 (top) and APOE4 (bottom) carriers. Slices 1 and 1′, ROIs for tau PET and BBB DCE-MRI scans, respectively (see e). e, Coronal 3D scans of regions studied in Fig. 2: HC (red), PHG (green), medial OFC (yellow), and ITG (blue). f, Correction of ¹⁸F-AV1451 off-target binding in the choroid plexus. Step 1, HC masks were generated from the 3D T1-weighted magnetization prepared–rapid gradient echo (MP-RAGE). Step 2, CP masks were generated from the T1-weighted VIBE post-GBCA image (flip angle, 15°). Step 3, HC and CP masks were overlaid (arrowheads, red). Step 4, areas of CP overlap with HC masks (arrowheads, yellow) were subtracted to obtain CP-corrected HC tau PET signal after adding 6-mm voxel size on top of CP mask generated from DCE data. g, Representative images of HC tau PET signal before (top) and after (bottom) applying the CP correction (arrows and white dotted lines show overlap between HC and CP).