Repeated intraperitoneal injection of liposomes containing phosphatidic acid and cardiolipin reduce β-amyloid levels in APP/PS1 transgenic mice

The accumulation of extracellular amyloid-beta (Aβ) peptide and intracellular neurofibrillary tangles in the brain are two major neuropathological hallmarks of Alzheimer's disease (AD). It is thought that an equilibrium exists between Aβ in the brain and in the peripheral blood and thus, it was...

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Detalles Bibliográficos
Autores: Ordóñez Gutiérrez, Lara, Wandosell, Francisco
Tipo de recurso: artículo
Fecha de publicación:2014
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/114301
Acceso en línea:https://hdl.handle.net/20.500.14352/114301
Access Level:acceso abierto
Palabra clave:616.894-053.9
Amyloid-beta
Alzheimer
Nanoparticles
APP/PS1
Ciencias Biomédicas
Ciencias
24 Ciencias de la Vida
32 Ciencias Médicas
Descripción
Sumario:The accumulation of extracellular amyloid-beta (Aβ) peptide and intracellular neurofibrillary tangles in the brain are two major neuropathological hallmarks of Alzheimer's disease (AD). It is thought that an equilibrium exists between Aβ in the brain and in the peripheral blood and thus, it was hypothesized that shifting this equilibrium towards the blood by enhancing peripheral clearance might reduce Aβ levels in the brain: the 'sink effect'. We tested this hypothesis by intraperitoneally injecting APP/PS1 transgenic mice with small unilamellar vesicles containing either phosphatidic acid or cardiolipin over 3weeks. This treatment reduced significantly the amount of Aβ in the plasma and the brain levels of Aβ were lighter affected. Nevertheless, this dosing regimen did modulate tau phosphorylation and glycogen synthase kinase 3 activities in the brain, suggesting that the targeting of circulating Aβ may be therapeutically relevant in AD.