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作者

Tong, Yawei Sun, Yang Tian, Xiaosheng

作者单位

Affiliations ¹ Neuroscience Research Institute and Department of Neurobiology, Key Laboratory for Neuroscience, Ministry of Education and Ministry of Public Health, Health Science Center, Peking University, Beijing, China. ² Department of Anesthesiology, Peking University Third Hospital, Beijing, China. ³ Department of Neurology, Peking University Third Hospital, Beijing, China dchui@bjmu.edu.cn dsfan@sina.com hanhongbin@bjmu.edu.cn sucunqin@hotmail.com. ⁴ Department of Radiology, Peking University Third Hospital, Beijing, China dchui@bjmu.edu.cn dsfan@sina.com hanhongbin@bjmu.edu.cn sucunqin@hotmail.com. ⁵ Key Laboratory of Atherosclerosis in Universities of Shandong, Institute of Atherosclerosis, Taishan Medical University, Taian, China, dchui@bjmu.edu.cn dsfan@sina.com hanhongbin@bjmu.edu.cn sucunqin@hotmail.com. ⁶ Neuroscience Research Institute and Department of Neurobiology, Key Laboratory for Neuroscience, Ministry of Education and Ministry of Public Health, Health Science Center, Peking University, Beijing, China, Department of Neurology, Peking University Third Hospital, Beijing, China dchui@bjmu.edu.cn dsfan@sina.com hanhongbin@bjmu.edu.cn sucunqin@hotmail.com.

刊名

HUMAN MOLECULAR GENETICS

年份

2015

卷号

Vol.24 No.19

页码

5388-5403

ISSN

0964-6906

关键词

NEUROTROPHIC FACTOR A-BETA COGNITIVE IMPAIRMENT AXONAL-TRANSPORT TRANSGENIC MICE GOLGI NETWORK CELL-DEATH IN-VIVO BRAIN METABOLISM

摘要

Abstract Phospholipid transfer protein 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 β in young and aged PLTP-deficient brains had been reported. However, the role of PLTP in amyloid precursor protein processing and Alzheimer's disease pathology remains elusive. Here we first found that deficiency of PLTP accelerated memory dysfunction in APP/PS1ΔE9 AD model mice ...更多

Abstract Phospholipid transfer protein 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 β in young and aged PLTP-deficient brains had been reported. However, the role of PLTP in amyloid precursor protein processing and Alzheimer's disease pathology remains elusive. Here we first found that deficiency of PLTP accelerated memory dysfunction in APP/PS1ΔE9 AD model mice at the age of 3 months. Further characterization showed that PLTP deficiency increased soluble Aβ peptides, and intracellular accumulation of Aβ was illustrated, which might be due to disrupted APP turnover and the enhanced amyloidogenic pathway. Besides, reduced brain-derived neurotrophic factor was found in PLTP-deficient APP/PS1ΔE9 mice, and the BDNF level was negatively correlated with Aβ42 content, instead of Aβ40 content. In addition, autophagic dysfunction was found in the PLTP-deficient APP/PS1ΔE9 mice. Our data presented a novel model to link phospholipid metabolism to APP processing and also suggested that PLTP played an important role in Aβ metabolism and would be useful to further elucidate functions of PLTP in AD susceptibility.收起

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