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- Title
Increased Amyloid-β Peptide-Induced Memory Deficits in Phospholipid Transfer Protein (PLTP) Gene Knockout Mice.
- Authors
Desrumaux, Catherine; Pisoni, Amandine; Meunier, Johann; Deckert, Valérie; Athias, Anne; Perrier, Véronique; Villard, Vanessa; Lagrost, Laurent; Verdier, Jean-Michel; Maurice, Tangui
- 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-β25-35 (Aβ25-35) peptide, a non-transgenic model of AD. Under basal conditions, PLTP-KO mice showed increased cerebral oxidative stress, increased brain Aβ1-42 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 Aβ25-35-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.
- Subjects
AMYLOID beta-protein; ALZHEIMER'S disease treatment; LIPID transfer protein; THERAPEUTIC use of vitamin E; OXIDATIVE stress; AMYLOID; ANTIOXIDANTS; PHOSPHOLIPIDS; THERAPEUTICS
- Publication
Neuropsychopharmacology, 2013, Vol 38, Issue 5, p817
- ISSN
0893-133X
- Publication type
Article
- DOI
10.1038/npp.2012.247