Oncotarget

Research Papers:

Deletion of plasma Phospholipid Transfer Protein (PLTP) increases microglial phagocytosis and reduces cerebral amyloid-β deposition in the J20 mouse model of Alzheimer's disease

Marine Mansuy, Stella Baille, Geoffrey Canet, Amélie Borie, Catherine Cohen-Solal, Michel Vignes, Véronique Perrier, Nathalie Chevallier, Naig Le Guern, Valérie Deckert, Laurent Lagrost, Laurent Givalois and Catherine Desrumaux _

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Oncotarget. 2018; 9:19688-19703. https://doi.org/10.18632/oncotarget.24802

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Abstract

Marine Mansuy1,2,3,4, Stella Baille1,2,3,4, Geoffrey Canet1,2,3,4, Amélie Borie1,2,3,4, Catherine Cohen-Solal5, Michel Vignes5, Véronique Perrier1,2,3,4, Nathalie Chevallier1,2,3,4, Naig Le Guern4,6,7, Valérie Deckert4,6,7, Laurent Lagrost4,6,7, Laurent Givalois1,2,3,4 and Catherine Desrumaux1,2,3,4

1Université Montpellier, Montpellier, F-34095 France

2Team ‘Environmental Impacts in Alzheimer’s disease and related disorders’ (EiAlz), Inserm, U1198, Montpellier, F-34095 France

3EPHE, Paris, F-75007 France

4LipSTIC LabEx, Fondation de Coopération Scientifique Bourgogne-Franche Comté, F-21000 Dijon, France

5UMR 5247, Max Mousseron Biomolecules Institute, 34095 Montpellier Cedex 5, France

6INSERM, LNC UMR1231, F-21000 Dijon, France

7University Bourgogne Franche-Comté, LNC UMR1231, F-21000 Dijon, France

Correspondence to:

Catherine Desrumaux, email: [email protected]

Keywords: phospholipid transfer protein; Alzheimer’s disease; innate immunity; phagocytosis; microglia

Received: January 26, 2018     Accepted: February 27, 2018     Published: April 13, 2018

ABSTRACT

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 Aβ deposits and astrogliosis, which can be explained at least in part by a rise of Aβ clearance through an increase in the microglial phagocytic activity and the expression of the Aβ-degrading enzyme neprilysin.

PLTP arises as a negative determinant of plaque clearance and over the lifespan, elevated PLTP activity could lead to a higher Aβ load in the brain.


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