机构：[1]Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing, China.[2]Mallinckrodt Institute of Radiology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA.[3]Harvard-MIT Program in Health Sciences and Technology, Harvard Medical School, Boston, MA, USA.[4]Department of Neurology, Washington in St. Louis University School of Medicine, St. Louis, MO, USA.
The objective of this study was to assess the association of sex and the apolipoprotein E (APOE) epsilon 4 allele with brain tau deposition and atrophy in older adults with Alzheimer's disease (AD) using quantitative F-18-AV-1451 positron emission tomography (PET) and magnetic resonance imaging (MRI). Methods: Preprocessed F-18-AV-1451 tau PET, raw T1-weighted structural MR images, demographic information, cerebrospinal fluid (CSF) total tau (t-tau) and phosphorylated tau (p-tau) measurements from 57 elderly individuals with AD were downloaded from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. An iteratively reblurred Van Cittert partial volume correction (PVC) method was applied to all preprocessed PET images. MRI images were used for PET spatial normalization and gray matter volume calculation. F-18-AV-1451 PET standardized uptake value ratio (SUVR) was calculated relative to the cerebellum gray matter. The effect of sex and APOE epsilon 4 status on SUVR and gray matter volume were assessed at both region of interest (ROI) and voxelwise levels. Results: Female APOE epsilon 4 carriers (FACs) had significant higher F-18-AV-1451 SUVRs in the lateral temporal, parietal, posterior cingulate, medial temporal, inferior temporal, entorhinal cortex, amygdala and parahippocampal gyrus regions, and exhibited smaller gray matter volumes in the posterior cingulate, medial temporal, inferior temporal and amygdala regions, as compared to the non-FACs (NFACs) comprised of female APOE epsilon 4 non-carriers, male APOE epsilon 4 carriers and male APOE epsilon 4 non-carriers. Voxelwise analysis revealed forebrain and limbic clusters with greater F-18-AV-1451 SUVRs and lower gray matter volume between FACs compared to the NFACs. Negative correlations between ROI F-18-AV-1451 SUVRs and gray matter volumes were significant after adjusting for age and years of education. Conclusions: Among elderly individuals with AD, sex modified the effects of the APOE epsilon 4 allele on region-specific tau deposition and gray matter volume. FACs had elevated brain region-specific tau PET SUVR and decreased gray matter volume in comparison to NFACs. The study provides a basis for the use of precision medicine in the diagnosis of AD and evaluation of therapeutics using F-18-AV-1451 PET and structural MRI.
基金：
Mallinckrodt Institute of Radiology, Washington University in St. Louis School of Medicine
第一作者机构：[1]Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing, China.[2]Mallinckrodt Institute of Radiology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA.
通讯作者：
通讯机构：[*1]Mallinckrodt Institute of Radiology, Washington University in St. Louis School of Medicine, 510 Kingshighway Blvd., St.Louis, MO 63110, USA[*2]Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing, China 45 Changchunjie, Xicheng District, Beijing 100053, China
推荐引用方式(GB/T 7714)：
Shaozhen Yan,Chaojie Zheng,Manish D Paranjpe,et al.Association of sex and APOE epsilon 4 with brain tau deposition and atrophy in older adults with Alzheimer's disease[J].THERANOSTICS.2020,10(23):10563-10572.doi:10.7150/thno.48522.
APA：
Shaozhen Yan,Chaojie Zheng,Manish D Paranjpe,Jian Li,Tammie L.S. Benzinger...&Yun Zhou.(2020).Association of sex and APOE epsilon 4 with brain tau deposition and atrophy in older adults with Alzheimer's disease.THERANOSTICS,10,(23)
MLA：
Shaozhen Yan,et al."Association of sex and APOE epsilon 4 with brain tau deposition and atrophy in older adults with Alzheimer's disease".THERANOSTICS 10..23(2020):10563-10572
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