title: Increased amyloid-β peptide-induced memory deficits in phospholipid transfer protein (PLTP) gene knockout mice.
abstract: Oxidative stress is recognized as one of the earliest and most intense pathological processes in Alzheimer's disease (AD), and the antioxidant vitamin E has been shown to efficiently prevent amyloid plaque formation and neurodegeneration. Plasma phospholipid transfer protein (PLTP) has a major role in vitamin E transfers in vivo, and PLTP deficiency in mice is associated with reduced brain vitamin E levels. To determine the impact of PLTP on amyloid pathology in vivo, we analyzed the vulnerability of PLTP-deficient (PLTP-KO) mice to the toxic effects induced by intracerebroventricular injection of oligomeric amyloid-β 25-35 (Aβ 25-35) peptide, a non-transgenic model of AD. Under basal conditions, PLTP-KO mice showed increased cerebral oxidative stress, increased brain Aβ 1-42 levels, and a lower expression of the synaptic function marker synaptophysin, as compared with wild-type mice. This PLTP-KO phenotype was associated with increased memory impairment 1 week after Aβ25-35 peptide injection. Restoration of brain vitamin E levels in PLTP-KO mice through a chronic dietary supplementation prevented Aβ 25-35-induced memory deficits and reduced cerebral oxidative stress and toxicity. We conclude that PLTP, through its ability to deliver vitamin E to the brain, constitutes an endogenous neuroprotective agent. Increasing PLTP activity may offer a new way to develop neuroprotective therapies.
authors.affiliation: INSERM U710, Université Montpellier 2, CC105, Place Eugène Bataillon, 34095 Montpellier, Cedex 05, France. Catherine.Desrumaux@univ-montp2.fr
authors.forename: Catherine
authors.initials: C
authors.lastname: Desrumaux
authors.forename: Amandine
authors.initials: A
authors.lastname: Pisoni
authors.forename: Johann
authors.initials: J
authors.lastname: Meunier
authors.forename: Valérie
authors.initials: V
authors.lastname: Deckert
authors.forename: Anne
authors.initials: A
authors.lastname: Athias
authors.forename: Véronique
authors.initials: V
authors.lastname: Perrier
authors.forename: Vanessa
authors.initials: V
authors.lastname: Villard
authors.forename: Laurent
authors.initials: L
authors.lastname: Lagrost
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Verdier
authors.forename: Tangui
authors.initials: T
authors.lastname: Maurice
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced* / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D010446:Peptide Fragments / Q000633:toxicity*; D010713:Phosphatidylcholines / Q000378:metabolism; D049294:Phospholipid Transfer Proteins / Q000172:deficiency*; D021641:Recognition, Psychology / Q000187:drug effects; D013109:Sphingomyelins / Q000378:metabolism; D024502:alpha-Tocopherol / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D010713:Phosphatidylcholines; D049294:Phospholipid Transfer Proteins; D013109:Sphingomyelins; C074636:amyloid beta-protein (25-35); D024502:alpha-Tocopherol