title: Phospholipid transfer protein (PLTP) deficiency accelerates memory dysfunction through altering amyloid precursor protein (APP) processing in a mouse model of Alzheimer's disease.
abstract: 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 β (Aβ) 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/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 (BDNF) 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.
authors.affiliation: 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.
authors.forename: Yawei
authors.initials: Y
authors.lastname: Tong
authors.affiliation: 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.
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.affiliation: 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.
authors.forename: Xiaosheng
authors.initials: X
authors.lastname: Tian
authors.affiliation: 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.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhou
authors.affiliation: 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.
authors.forename: Hecheng
authors.initials: H
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhan
authors.affiliation: 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.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.affiliation: 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.
authors.forename: Bolati
authors.initials: B
authors.lastname: Kuerban
authors.affiliation: Department of Anesthesiology, Peking University Third Hospital, Beijing, China.
authors.forename: Zhengqian
authors.initials: Z
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Qiudian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Yinglan
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Neurology, Peking University Third Hospital, Beijing, China dchui@bjmu.edu.cn dsfan@sina.com hanhongbin@bjmu.edu.cn sucunqin@hotmail.com.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Fan
authors.affiliation: Department of Anesthesiology, Peking University Third Hospital, Beijing, China.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Radiology, Peking University Third Hospital, Beijing, China dchui@bjmu.edu.cn dsfan@sina.com hanhongbin@bjmu.edu.cn sucunqin@hotmail.com.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Han
authors.affiliation: 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.
authors.forename: Shucun
authors.initials: S
authors.lastname: Qin
authors.affiliation: 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.
authors.forename: Dehua
authors.initials: D
authors.lastname: Chui
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D001343:Autophagy; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D004195:Disease Models, Animal; D055786:Gene Knockout Techniques; D006801:Humans; D008569:Memory Disorders / Q000235:genetics*; D051379:Mice; D049294:Phospholipid Transfer Proteins / Q000172:deficiency*
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D019208:Brain-Derived Neurotrophic Factor; D049294:Phospholipid Transfer Proteins; C510091:phospholipid transfer protein, mouse