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学科主题基础医学
Phospholipid transfer protein (PLTP) deficiency accelerates memory dysfunction through altering amyloid precursor protein (APP) processing in a mouse model of Alzheimer′s disease
Tong, Yawei1,2,3; Sun, Yang1,2,3; Tian, Xiaosheng1,2,3; Zhou, Ting1,2,3; Wang, Hecheng1,2,3; Zhang, Tao1,2,3; Zhan, Rui1,2,3; Zhao, Lei1,2,3; Kuerban, Bolati1,2,3; Li, Zhengqian6; Wang, Qiudian1,2,3; Jin, Yinglan1,2,3; Fan, Dongsheng5; Guo, Xiangyang6; Han, Hongbin7; Qin, Shucun4; Chui, Dehua1,2,3,5
刊名HUMAN MOLECULAR GENETICS
2015-10-01
DOI10.1093/hmg/ddv262
24期:19页:5388-5403
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology ; Genetics & Heredity
研究领域[WOS]Biochemistry & Molecular Biology ; Genetics & Heredity
关键词[WOS]Neurotrophic Factor ; A-beta ; Cognitive Impairment ; Axonal-transport ; Transgenic Mice ; Golgi Network ; Cell-death ; In-vivo ; Brain ; Metabolism
英文摘要

Phospholipid transfer protein (PLTP) is a widely expressed lipid transfer protein participating in the transport of cholesterol and other lipids in the plasma and peripheral tissues. Recently, elevated amyloid beta (A beta) in young and aged PLTP-deficient brains had been reported. However, the role of PLTP in amyloid precursor protein (APP) processing and Alzheimer′s disease (AD) pathology remains elusive. Here we first found that deficiency of PLTP accelerated memory dysfunction in APP/PS1 Delta E9 AD model mice at the age of 3 months. Further characterization showed that PLTP deficiency increased soluble A beta peptides, and intracellular accumulation of A beta was illustrated, which might be due to disrupted APP turnover and the enhanced amyloidogenic pathway. Besides, reduced brain-derived neurotrophic factor (BDNF) was found in PLTP-deficient APP/PS1 Delta E9 mice, and the BDNF level was negatively correlated with A beta 42 content, instead of A beta 40 content. In addition, autophagic dysfunction was found in the PLTP-deficient APP/PS1 Delta E9 mice. Our data presented a novel model to link phospholipid metabolismto APP processing and also suggested that PLTP played an important role in A beta metabolism and would be useful to further elucidate functions of PLTP in AD susceptibility.

语种英语
WOS记录号WOS:000363018100003
通讯作者邮箱dsfan@sina.com
项目编号2012CB911000 ; 2012CB911004 ; 81171015 ; 81371205 ; 61450004
资助机构National High Technology Research and Development Program of China (973 Program) ; National Natural Science Foundation of China (NSFC)
引用统计
被引频次:3[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/59114
专题北京大学基础医学院_神经生物学系
北京大学第一临床医学院_手术室
北京大学第二临床医学院_检验科
北京大学第三临床医学院_麻醉科
北京大学第三临床医学院_神经内科
作者单位1.Peking Univ, Hlth Sci Ctr, Neurosci Res Inst, Beijing 100191, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Dept Neurobiol, Key Lab Neurosci,Minist Educ, Beijing 100191, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Minist Publ Hlth, Beijing 100191, Peoples R China
4.Taishan Med Univ, Shandong Univ, Inst Atherosclerosis, Key Lab Atherosclerosis, Tai An, Shandong, Peoples R China
5.Peking Univ, Hosp 3, Dept Neurol, Beijing 100871, Peoples R China
6.Peking Univ, Hosp 3, Dept Anesthesiol, Beijing 100871, Peoples R China
7.Peking Univ, Hosp 3, Dept Radiol, Beijing 100871, Peoples R China
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Tong, Yawei,Sun, Yang,Tian, Xiaosheng,等. Phospholipid transfer protein (PLTP) deficiency accelerates memory dysfunction through altering amyloid precursor protein (APP) processing in a mouse model of Alzheimer′s disease[J]. HUMAN MOLECULAR GENETICS,2015,24(19):5388-5403.
APA Tong, Yawei.,Sun, Yang.,Tian, Xiaosheng.,Zhou, Ting.,Wang, Hecheng.,...&Chui, Dehua.(2015).Phospholipid transfer protein (PLTP) deficiency accelerates memory dysfunction through altering amyloid precursor protein (APP) processing in a mouse model of Alzheimer′s disease.HUMAN MOLECULAR GENETICS,24(19),5388-5403.
MLA Tong, Yawei,et al."Phospholipid transfer protein (PLTP) deficiency accelerates memory dysfunction through altering amyloid precursor protein (APP) processing in a mouse model of Alzheimer′s disease".HUMAN MOLECULAR GENETICS 24.19(2015):5388-5403.
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