PMID- 26160914
OWN - NLM
STAT- MEDLINE
DCOM- 20160706
LR  - 20210218
IS  - 1460-2083 (Electronic)
IS  - 0964-6906 (Linking)
VI  - 24
IP  - 19
DP  - 2015 Oct 1
TI  - Phospholipid transfer protein (PLTP) deficiency accelerates memory dysfunction 
      through altering amyloid precursor protein (APP) processing in a mouse model of 
      Alzheimer's disease.
PG  - 5388-403
LID - 10.1093/hmg/ddv262 [doi]
AB  - 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 (Abeta) 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/PS1DeltaE9 AD model mice at the age of 3 months. Further 
      characterization showed that PLTP deficiency increased soluble Abeta peptides, and 
      intracellular accumulation of Abeta 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/PS1DeltaE9 
      mice, and the BDNF level was negatively correlated with Abeta42 content, instead of 
      Abeta40 content. In addition, autophagic dysfunction was found in the PLTP-deficient 
      APP/PS1DeltaE9 mice. Our data presented a novel model to link phospholipid metabolism 
      to APP processing and also suggested that PLTP played an important role in Abeta 
      metabolism and would be useful to further elucidate functions of PLTP in AD 
      susceptibility.
CI  - (c) The Author 2015. Published by Oxford University Press. All rights reserved. For 
      Permissions, please email: journals.permissions@oup.com.
FAU - Tong, Yawei
AU  - Tong Y
AD  - 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.
FAU - Sun, Yang
AU  - Sun Y
AD  - 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.
FAU - Tian, Xiaosheng
AU  - Tian X
AD  - 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.
FAU - Zhou, Ting
AU  - Zhou T
AD  - 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.
FAU - Wang, Hecheng
AU  - Wang H
AD  - 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.
FAU - Zhang, Tao
AU  - Zhang T
AD  - 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.
FAU - Zhan, Rui
AU  - Zhan R
AD  - 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.
FAU - Zhao, Lei
AU  - Zhao L
AD  - 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.
FAU - Kuerban, Bolati
AU  - Kuerban B
AD  - 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.
FAU - Li, Zhengqian
AU  - Li Z
AD  - Department of Anesthesiology, Peking University Third Hospital, Beijing, China.
FAU - Wang, Qiudian
AU  - Wang Q
AD  - 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.
FAU - Jin, Yinglan
AU  - Jin Y
AD  - 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.
FAU - Fan, Dongsheng
AU  - Fan D
AD  - Department of Neurology, Peking University Third Hospital, Beijing, China 
      dchui@bjmu.edu.cn dsfan@sina.com hanhongbin@bjmu.edu.cn sucunqin@hotmail.com.
FAU - Guo, Xiangyang
AU  - Guo X
AD  - Department of Anesthesiology, Peking University Third Hospital, Beijing, China.
FAU - Han, Hongbin
AU  - Han H
AD  - Department of Radiology, Peking University Third Hospital, Beijing, China 
      dchui@bjmu.edu.cn dsfan@sina.com hanhongbin@bjmu.edu.cn sucunqin@hotmail.com.
FAU - Qin, Shucun
AU  - Qin S
AD  - 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.
FAU - Chui, Dehua
AU  - Chui D
AD  - 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.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150709
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (APP protein, human)
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Phospholipid Transfer Proteins)
RN  - 0 (phospholipid transfer protein, mouse)
SB  - IM
MH  - Alzheimer Disease/genetics/metabolism/*physiopathology
MH  - Amyloid beta-Peptides/metabolism
MH  - Amyloid beta-Protein Precursor/*metabolism
MH  - Animals
MH  - Autophagy
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Disease Models, Animal
MH  - Gene Knockout Techniques
MH  - Humans
MH  - Memory Disorders/*genetics
MH  - Mice
MH  - Phospholipid Transfer Proteins/*deficiency
EDAT- 2015/07/15 06:00
MHDA- 2016/07/07 06:00
CRDT- 2015/07/11 06:00
PHST- 2015/05/01 00:00 [received]
PHST- 2015/07/06 00:00 [accepted]
PHST- 2015/07/11 06:00 [entrez]
PHST- 2015/07/15 06:00 [pubmed]
PHST- 2016/07/07 06:00 [medline]
AID - ddv262 [pii]
AID - 10.1093/hmg/ddv262 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2015 Oct 1;24(19):5388-403. doi: 10.1093/hmg/ddv262. Epub 2015 Jul 
      9.