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Sex modulates the ApoE epsilon 4 effect on brain tau deposition measured by F-18-AV-1451 PET in individuals with mild cognitive impairment

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收录情况： ◇ SCIE

作者：
Liu, Min[1,2] * ; Paranjpe, Manish D.[3] * ; Zhou, Xin[4] ; Duy, Phan Q.[5] ; Goyal, Manu S.[6] ; Benzinger, Tammie L. S.[6] ; Lu, Jie[7] ; Wang, Rongfu[1,*2] ; Zhou, Yun[1,2,6,*1] ;
机构： [1]Department of Nuclear Medicine, Peking University First Hospital, Beijing, China [2]The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America [3]Harvard-MIT Program in Health Sciences and Technology, Harvard Medical School, Boston, MA, United States of America [4]Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA, United States of America [5]Medical Scientist Training Program, Yale University School of Medicine, New Haven, CT, United States of America [6]Mallinckrodt Institute of Radiology, Washington University in St. Louis School of Medicine, St. Louis, MO, United States of America [7]Department of Radiology, Xuanwu Hospital of Capital Medical University, Beijing, China
出处：
DOI： 10.7150/thno.35366
ISSN：

关键词： tau deposition ApoE epsilon 4 mild cognitive impairment F-18-AV-1451 partial volume correction

摘要：
The strongest genetic risk factor for Alzheimer's disease (AD) is the Apolipoprotein E type 4 allele (ApoE epsilon 4). The interaction between sex and ApoE epsilon 4 carrier status on AD risk remains an area of intense investigation. We hypothesized that sex modulates the relationship between ApoE epsilon 4 carrier status and brain tau deposition (a quantitative endophenotype in AD) in individuals with mild cognitive impairment (MCI). Methods: Preprocessed F-18-AV-1451 tau and F-18-AV-45 amyloid PET images, T1-weighted structural magnetic resonance imaging (MRI) scans, demographic information, and cerebrospinal fluid (CSF) total tau (t-tau) and phosphorylated tau (p-tau) measurements from 108 MCI subjects in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were included. After downloading pre-processed images from ADNI, an iterative reblurred Van Cittertiteration partial volume correction (PVC) method was applied to all PET images. MRIs were used for PET spatial normalization. Regions of interest (ROIs) were defined in standard space, and standardized uptake value ratio (SUVR) images relative to cerebellum were computed. ApoE epsilon 4 by sex interaction analyses on F-18-AV-1451 and CSF tau (t-tau, p-tau) were assessed using generalized linear models. The association between F-18-AV-1451 SUVR and CSF tau (t-tau, p-tau) was assessed. Results: After applying PVC and controlling for age, education level and global cortical F-18-AV-45 SUVR, we found that the entorhinal cortex, amygdala, parahippocampal gyrus, posterior cingulate, and occipital ROIs exhibited a significant ApoE epsilon 4 by sex interaction effect (false discovery rate P < 0.1) among MCI individuals. We also found a significant ApoE epsilon 4 by sex interaction effect on CSF t-tau and p-tau. F-18-AV-1451 SUVR in the 5 ROIs with ApoE epsilon 4 by sex interaction was significantly correlated with CSF p-tau and t-tau. Conclusions: Our findings suggest that women are more susceptible to ApoE epsilon 4-associated accumulation of neurofibrillary tangles in MCI compared to males. Both CSF tau (p-tau, t-tau) and brain tau PET are robust quantitative biomarkers for studying ApoE epsilon 4 by sex effects on brain tau deposition in MCI participants.

基金：
Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]; DOD ADNI (Department of Defense) [W81XWH-12-2-0012]; China Scholarship Council; NIH Medical Scientist Training Program Training grant [T32GM007205]
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外文
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PubmedID：
中科院(CAS)分区：
出版当年[2018]版：
大类 | 1 区 医学
小类 | 1 区 医学：研究与实验
最新[2023]版：
大类 | 1 区 医学
小类 | 1 区 医学：研究与实验
JCR分区：
出版当年[2017]版：
Q1 MEDICINE, RESEARCH & EXPERIMENTAL
最新[2023]版：
Q1 MEDICINE, RESEARCH & EXPERIMENTAL

影响因子： 最新[2023版] 最新五年平均 出版当年[2017版] 出版当年五年平均 出版前一年[2016版] 出版后一年[2018版]

第一作者：
第一作者机构： [1]Department of Nuclear Medicine, Peking University First Hospital, Beijing, China [2]The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America
共同第一作者：
通讯作者：
通讯机构： [1]Department of Nuclear Medicine, Peking University First Hospital, Beijing, China [2]The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America [6]Mallinckrodt Institute of Radiology, Washington University in St. Louis School of Medicine, St. Louis, MO, United States of America [*1]Mallinckrodt Institute of Radiology, Washington University in St. Louis School of Medicine, 510 Kingshighway Blvd., St. Louis, MO 63110, USA [*2]Department of Nuclear Medicine, Peking University First Hospital, No. 8 Xishiku St., Xicheng District, Beijing, 100034, China
推荐引用方式(GB/T 7714)：
Liu Min,Paranjpe Manish D.,Zhou Xin,et al.Sex modulates the ApoE epsilon 4 effect on brain tau deposition measured by F-18-AV-1451 PET in individuals with mild cognitive impairment[J].THERANOSTICS.2019,9(17):4959-4970.doi:10.7150/thno.35366.
APA：
Liu, Min,Paranjpe, Manish D.,Zhou, Xin,Duy, Phan Q.,Goyal, Manu S....&Zhou, Yun.(2019).Sex modulates the ApoE epsilon 4 effect on brain tau deposition measured by F-18-AV-1451 PET in individuals with mild cognitive impairment.THERANOSTICS,9,(17)
MLA：
Liu, Min,et al."Sex modulates the ApoE epsilon 4 effect on brain tau deposition measured by F-18-AV-1451 PET in individuals with mild cognitive impairment".THERANOSTICS 9..17(2019):4959-4970

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