TY - JOUR T1 - <strong>Precision imaging the association of sex and APOE ε4 with brain tau deposition in individuals with Alzheimer’s disease using <sup>18</sup>F-AV-1451 PET</strong> JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 280 LP - 280 VL - 61 IS - supplement 1 AU - Shaozhen Yan AU - Chaojie Zheng AU - Jian Li AU - Gengsheng Chen AU - Zhude Tu AU - Joel Perlmutter AU - Tammie Benzinger AU - Jie Lu AU - Yun Zhou Y1 - 2020/05/01 UR - http://jnm.snmjournals.org/content/61/supplement_1/280.abstract N2 - 280Objectives: Apolipoprotein E type 4 allele (APOE ε4) is a strongest genetic risk factor for Alzheimer’s disease (AD). Recent 18F-AV-1451 Tau PET studies show that the APOE ε4 effects on brain region-specific tau deposition is modulated by sex in cognitively normal and older adults with mild cognitive impairment (MCI). The objective of the study is to examine the association of sex and APOE ε4 on brain tau deposition in individuals with AD using quantitative 18F-AV-1451 PET. Methods: Preprocessed 18F-AV-1451 tau and 18F-AV-45 amyloid PET images, 3D-T1-weighted structural MR images, demographic information, and of β-amyloid 42, CSF t-tau and phosphorylated tau (p-tau) measurements from 39 AD subjects in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database were included. An iterative reblurred Van Cittertiteration partial volume correction (PVC) method was applied to all preprocessed PET images. T1 images were used for PET spatial normalization. Regions of interest (ROIs) were defined in MNI standard space, and standardized uptake value ratio (SUVR) relative to cerebellum were computed. ApoE ε4 by sex interaction analyses on 18F-AV-1451 tau deposition were assessed using a generalized linear model: ROI_SUVR (18F-AV-1451) ~ Age + Educational level + Global cortex_SUVR (18F-AV-45) + Sex:APOE ε4 status. Stratified analysis on ApoE ε4 and sex interaction was performed on both ROI and voxelwise levels. SPM and SAS software were used for image processing and statistical analysis. Results: Of the 39 AD patients, 17 were women and 21were APOE ε4 carriers. In stratified analysis of sex and APOE ε4, women with APOE ε4 carriers exhibited highest tau deposition than other 3 sub-groups (Figure 1). After PVC and controlling for age, education level and global cortical 18F-AV-45 SUVR, we found that the parietal, post precuneus, entorhinal cortex, amygdala, parahippocampal gyrus, posterior cingulate, and medial temporal ROIs exhibited a significant ApoE ε4 by sex interaction effect in AD individuals (P &lt; 0.05) (Figure 2). Conclusions: Our findings first demonstrate that women are more affected than men with ApoE ε4-associated region-specific accumulation of neurofibrillary tangles in elders with AD. Brain tau PET is robust quantitative biomarkers for studying APOE ε4 by sex effects on brain tau deposition in AD participants.Figure 1. Mean 18F-AV-1451 PET SUVR images in AD individuals. Mean images were generated by computing the mean of SUVR images with partial volume correction.Figure 2. Regions with significant ApoE ε4 effect on 18F-AV-1451 SUVR in AD participants. Bar graphs showing ROIs SUVR (mean with error bars depicting SD) of 18F-AV-1451 tau PET imaging between APOE ε4 carriers and non-carriers in regions with significant APOE ε4 effect. P value were defined using a two-sample t-test to compare SUVR between APOE ε4 carriers and APOE ε4 non-carriers in men and women subgroups, and between men and women in APOE ε4 carrier and APOE ε4 non-carrier subgroups. *** P &lt; 0.001, ** P &lt; 0.01, * P &lt; 0.05. ER -