| First Author | Mansuy M | Year | 2018 |
| Journal | Oncotarget | Volume | 9 |
| Issue | 28 | Pages | 19688-19703 |
| PubMed ID | 29731975 | Mgi Jnum | J:298183 |
| Mgi Id | MGI:6457217 | Doi | 10.18632/oncotarget.24802 |
| Citation | Mansuy M, et al. (2018) Deletion of plasma Phospholipid Transfer Protein (PLTP) increases microglial phagocytosis and reduces cerebral amyloid-beta deposition in the J20 mouse model of Alzheimer's disease. Oncotarget 9(28):19688-19703 |
| abstractText | Plasma phospholipid transfer protein (PLTP) binds and transfers a number of amphipathic compounds, including phospholipids, cholesterol, diacylglycerides, tocopherols and lipopolysaccharides. PLTP functions are relevant for many pathophysiological alterations involved in neurodegenerative disorders (especially lipid metabolism, redox status, and immune reactions), and a significant increase in brain PLTP levels was observed in patients with Alzheimer's disease (AD) compared to controls. To date, it has not been reported whether PLTP can modulate the formation of amyloid plaques, i.e. one of the major histopathological hallmarks of AD. We thus assessed the role of PLTP in the AD context by breeding PLTP-deficient mice with an established model of AD, the J20 mice. A phenotypic characterization of the amyloid pathology was conducted in J20 mice expressing or not PLTP. We showed that PLTP deletion is associated with a significant reduction of cerebral Abeta deposits and astrogliosis, which can be explained at least in part by a rise of Abeta clearance through an increase in the microglial phagocytic activity and the expression of the Abeta-degrading enzyme neprilysin. PLTP arises as a negative determinant of plaque clearance and over the lifespan, elevated PLTP activity could lead to a higher Abeta load in the brain. |
