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In April 2021, the team of Professor Lu Jie from Xuanwu Hospital of Capital Medical University published a research paper entitled "Sex modifies APOE ε4 dose effect on brain taudeposition in cognitively impaired individuals" online on BRAIN.
The study found that there are gender differences in the effects of Alzheimer's disease (AD) high-risk gene APOE ε4 on brain tau protein aggregation, which provides imaging evidence for the incidence of AD in females than in males.
The first author of the paper is Dr.
Yan Shaozhen, and the corresponding authors are Professor Lu Jie and Professor Zhou Yun.
Research Introduction AD is the most common type of Alzheimer’s.
APOE ε4 is the biggest genetic risk factor for AD.
Abnormal accumulation of tau protein in the brain is one of the characteristic pathological changes of AD.
Gender differences in the prevalence of AD have been paid more and more attention, but the gender differences in the clinical pathological basis have not received too much attention.
The latest research shows that brain tau protein aggregation is related to the dose of APOE ε4 in the normal elderly population, but it is still unknown whether there is a gender difference between the APOE ε4 dose of AD patients and the brain tau protein aggregation.
This study included 268 patients with cognitive impairment (146 cases of APOE ε4 non-carriers, 85 cases of APOE ε4 heterozygotes, and 37 cases of APOE ε4 homozygotes).
The 18F-flortaucipir PET was used in 12 cortical and subcortical regions of interest.
(ROIs) Quantify tau protein.
Firstly, a linear mixed model was used to analyze the effect of APOE ε4 dose on tau aggregation in different ROIs.
With age, gender, and Aβ deposition in the whole brain as covariates, the results showed that the tau aggregation in the brains of APOE ε4 carriers was significantly higher than that of non-carriers.
There is no dose effect of APOE ε4 for tau aggregation.Based on this, the interaction between APOE ε4 dose and gender on tau aggregation was further analyzed at the ROI and voxel level.
With age, gender, and Aβ deposition in the whole brain as covariates, it was found that the effect of APOE ε4 dose effect on tau aggregation was found in men.
Among patients, there was no statistically significant difference in the increase in tau aggregation between heterozygotes and homozygotes of female APOE ε4.
Figure 1 18F-flortaucipirtau PET image shows that APOE ε4 dose and tau accumulation in the brain of patients with cognitive impairment of different genders Figure 2 APOE ε4 dose effect has gender differences in the impact of tau accumulation in the brain.
The tau aggregation of male APOE ε4 homozygotes was significantly higher than that of heterozygotes and non-carriers.
There was no significant difference in tau aggregation between APOE ε4 heterozygotes and non-carriers.
Female APOE ε4 homozygous and heterozygous tau accumulation is significantly higher than APOE ε4 non-carriers, APOE ε4 homozygous and heterozygous tau aggregation has no significant difference.
This study clarified that the APOE ε4 dose effect has gender differences in the impact of APOE ε4 on brain tau aggregation.
The research results reveal the reasons why women are more likely to suffer from AD, provide a more comprehensive theoretical framework for understanding the complex pathogenesis of AD, and have important guiding significance for further promoting the precise treatment of AD.
Expert profile Professor Lu Jie, chief physician, professor, doctoral tutor, winner of the National Natural Science Outstanding Youth Fund, and a leader in scientific and technological innovation of the National "Ten Thousand Talents Program".
Current Deputy Dean of Xuanwu Hospital of Capital Medical University, Director of Department of Radiology and Nuclear Medicine, Xuanwu Hospital of Capital Medical University, Deputy Director of Beijing Key Laboratory of Magnetic Resonance Imaging Brain Informatics, and Cerebral Hemodynamics, Stroke Institute, Beijing Institute of Critical Brain Diseases Director of Science Research Office.
Mainly engaged in the research of brain disease function and molecular imaging, presided over 17 projects including the 13th Five-Year Key Special Project of the Ministry of Science and Technology, National Natural Science Foundation of China; published more than 100 SCI papers in top international journals such as Neuron, BRAIN, and Nature Communications; Translation) 8 books.
Main academic appointments: National member of Radiology Branch of Chinese Medical Association, Vice Chairman of Radiology Branch of Chinese Medical Imaging Technology Research Association, Deputy Chairman of Radiology Branch of Beijing Medical Association, Vice Chairman of Radiologist Branch of Beijing Medical Association, Neurosci Biobehav Rev, Neuroimage , JAD and other magazine review experts.
Expert profile Dr.
Yan Shaozhen, Department of Radiology and Nuclear Medicine, Xuanwu Hospital of Capital Medical University, Physician, Ph.
D.
During his Ph.
D.
, he studied at Washington University in St.
Louis for 1 year.
His graduation thesis was awarded as "Excellent Doctoral Dissertation of Capital Medical University".
The main research direction is the nervous system PET/MR research.
As the first author, he published 4 SCI papers in journals such as BRAIN, and won the SNMMI “The International Best Abstract Award” in 2019 and the SNMMI “1st Place of the Poster Award” in 2020.
Compiled 1 book, presided over 1 academic-level project, participated in 2 projects including the National Natural Science Foundation of China.
References: [1] Shaozhen Yan, Chaojie Zheng, Manish D Paranjpe, Yanxiao Li, Weihua Li, Xiuying Wang, Tammie LS Benzinger, Jie Lu, Yun Zhou, the Alzheimer's Disease Neuroimaging Initiative, Sex modifies APOE ε4 dose effect on brain tau deposition in cognitively impaired individuals, Brain, 2021;, awab160, https://doi.
org/10.
1093/brain/awab160[2] Official account of Xuanwu Hospital, Capital Medical University
The study found that there are gender differences in the effects of Alzheimer's disease (AD) high-risk gene APOE ε4 on brain tau protein aggregation, which provides imaging evidence for the incidence of AD in females than in males.
The first author of the paper is Dr.
Yan Shaozhen, and the corresponding authors are Professor Lu Jie and Professor Zhou Yun.
Research Introduction AD is the most common type of Alzheimer’s.
APOE ε4 is the biggest genetic risk factor for AD.
Abnormal accumulation of tau protein in the brain is one of the characteristic pathological changes of AD.
Gender differences in the prevalence of AD have been paid more and more attention, but the gender differences in the clinical pathological basis have not received too much attention.
The latest research shows that brain tau protein aggregation is related to the dose of APOE ε4 in the normal elderly population, but it is still unknown whether there is a gender difference between the APOE ε4 dose of AD patients and the brain tau protein aggregation.
This study included 268 patients with cognitive impairment (146 cases of APOE ε4 non-carriers, 85 cases of APOE ε4 heterozygotes, and 37 cases of APOE ε4 homozygotes).
The 18F-flortaucipir PET was used in 12 cortical and subcortical regions of interest.
(ROIs) Quantify tau protein.
Firstly, a linear mixed model was used to analyze the effect of APOE ε4 dose on tau aggregation in different ROIs.
With age, gender, and Aβ deposition in the whole brain as covariates, the results showed that the tau aggregation in the brains of APOE ε4 carriers was significantly higher than that of non-carriers.
There is no dose effect of APOE ε4 for tau aggregation.Based on this, the interaction between APOE ε4 dose and gender on tau aggregation was further analyzed at the ROI and voxel level.
With age, gender, and Aβ deposition in the whole brain as covariates, it was found that the effect of APOE ε4 dose effect on tau aggregation was found in men.
Among patients, there was no statistically significant difference in the increase in tau aggregation between heterozygotes and homozygotes of female APOE ε4.
Figure 1 18F-flortaucipirtau PET image shows that APOE ε4 dose and tau accumulation in the brain of patients with cognitive impairment of different genders Figure 2 APOE ε4 dose effect has gender differences in the impact of tau accumulation in the brain.
The tau aggregation of male APOE ε4 homozygotes was significantly higher than that of heterozygotes and non-carriers.
There was no significant difference in tau aggregation between APOE ε4 heterozygotes and non-carriers.
Female APOE ε4 homozygous and heterozygous tau accumulation is significantly higher than APOE ε4 non-carriers, APOE ε4 homozygous and heterozygous tau aggregation has no significant difference.
This study clarified that the APOE ε4 dose effect has gender differences in the impact of APOE ε4 on brain tau aggregation.
The research results reveal the reasons why women are more likely to suffer from AD, provide a more comprehensive theoretical framework for understanding the complex pathogenesis of AD, and have important guiding significance for further promoting the precise treatment of AD.
Expert profile Professor Lu Jie, chief physician, professor, doctoral tutor, winner of the National Natural Science Outstanding Youth Fund, and a leader in scientific and technological innovation of the National "Ten Thousand Talents Program".
Current Deputy Dean of Xuanwu Hospital of Capital Medical University, Director of Department of Radiology and Nuclear Medicine, Xuanwu Hospital of Capital Medical University, Deputy Director of Beijing Key Laboratory of Magnetic Resonance Imaging Brain Informatics, and Cerebral Hemodynamics, Stroke Institute, Beijing Institute of Critical Brain Diseases Director of Science Research Office.
Mainly engaged in the research of brain disease function and molecular imaging, presided over 17 projects including the 13th Five-Year Key Special Project of the Ministry of Science and Technology, National Natural Science Foundation of China; published more than 100 SCI papers in top international journals such as Neuron, BRAIN, and Nature Communications; Translation) 8 books.
Main academic appointments: National member of Radiology Branch of Chinese Medical Association, Vice Chairman of Radiology Branch of Chinese Medical Imaging Technology Research Association, Deputy Chairman of Radiology Branch of Beijing Medical Association, Vice Chairman of Radiologist Branch of Beijing Medical Association, Neurosci Biobehav Rev, Neuroimage , JAD and other magazine review experts.
Expert profile Dr.
Yan Shaozhen, Department of Radiology and Nuclear Medicine, Xuanwu Hospital of Capital Medical University, Physician, Ph.
D.
During his Ph.
D.
, he studied at Washington University in St.
Louis for 1 year.
His graduation thesis was awarded as "Excellent Doctoral Dissertation of Capital Medical University".
The main research direction is the nervous system PET/MR research.
As the first author, he published 4 SCI papers in journals such as BRAIN, and won the SNMMI “The International Best Abstract Award” in 2019 and the SNMMI “1st Place of the Poster Award” in 2020.
Compiled 1 book, presided over 1 academic-level project, participated in 2 projects including the National Natural Science Foundation of China.
References: [1] Shaozhen Yan, Chaojie Zheng, Manish D Paranjpe, Yanxiao Li, Weihua Li, Xiuying Wang, Tammie LS Benzinger, Jie Lu, Yun Zhou, the Alzheimer's Disease Neuroimaging Initiative, Sex modifies APOE ε4 dose effect on brain tau deposition in cognitively impaired individuals, Brain, 2021;, awab160, https://doi.
org/10.
1093/brain/awab160[2] Official account of Xuanwu Hospital, Capital Medical University
