title: PLTP deficiency impairs learning and memory capabilities partially due to alteration of amyloid-β metabolism in old mice.
abstract: Increased expression of phospholipid transfer protein (PLTP) was observed in the brains of Alzheimer's disease (AD) patients; however, the role of PLTP in the progress of AD is still poorly understood. The objective of this study was to evaluate the effect of PLTP deficiency on the recognition and metabolism of amyloid-β (Aβ) in mice. We performed the Morris water maze to determine the learning and memory capabilities of 50-week age wild type mice (WT, n = 12) and PLTP knockout mice (PLTP-/-, n = 12). The levels of Aβ and amyloid-β protein precursor (AβPP) were examined by ELISA and western blot, respectively. The levels and activity of β- and γ-secretases were determined by western blot and activity assay kit, respectively. Morris water maze results showed that PLTP deficiency significantly impaired recognition compared with WT mice. Levels of Aβ42 in the cortex and hippocampus was significantly increased, yet the levels of Aβ40 in the cortex was decreased in PLTP-/- compared with WT mice. No typical senile plaques were found in the WT or PLTP-/- mice. AβPP expression and β-secretase activity were both significantly increased in PLTP-/- mice. Moreover, PLTP deficiency increased the expression of γ-secretase catalytic units and decreased the content of apolipoprotein E. Therefore we concluded that PLTP deficiency impaired cognition and aggravated AD by enhancing the generation of Aβ in the cortex of old mice.
authors.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong; Institute of Atherosclerosis, Taishan Medical University, Taian, China School of Pharmaceutical Science, Taishan Medical University, Taian, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong; Institute of Atherosclerosis, Taishan Medical University, Taian, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: School of Pharmaceutical Science, Taishan Medical University, Taian, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong; Institute of Atherosclerosis, Taishan Medical University, Taian, China.
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong; Institute of Atherosclerosis, Taishan Medical University, Taian, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Luo
authors.affiliation: School of Pharmaceutical Science, Taishan Medical University, Taian, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Anatomy and Cell Biology, SUNY Downstate Medical Center, New York, USA.
authors.forename: Xian-Cheng
authors.initials: XC
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong; Institute of Atherosclerosis, Taishan Medical University, Taian, China.
authors.forename: Shucun
authors.initials: S
authors.lastname: Qin
mesh_terms: D000375:Aging / Q000502:physiology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D018782:Maze Learning / Q000502:physiology*; D008569:Memory Disorders / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D049294:Phospholipid Transfer Proteins / Q000172:deficiency*; D058225:Plaque, Amyloid / Q000473:pathology
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D049294:Phospholipid Transfer Proteins; C510091:phospholipid transfer protein, mouse
keywords: Amyloid-β; amyloid-β protein precursor; capabilities of learning and memory; phospholipid transfer protein