Intravenous treatment with human recombinant ApoA-I Milano reduces beta amyloid cerebral deposition in the APP23-transgenic mouse model of Alzheimer's disease

• Verfasst von: Fernández de Retana Alda, Sofía [VerfasserIn]
• Verfasst von: Fatar, Marc [VerfasserIn]
• Verfasst von: Grudzenski-Theis, Saskia [VerfasserIn]
• Titel: Intravenous treatment with human recombinant ApoA-I Milano reduces beta amyloid cerebral deposition in the APP23-transgenic mouse model of Alzheimer's disease
• Verf.angabe: Sofía Fernández-de Retana, Alex Montañola, Paula Marazuela, Maialen De La Cuesta, Aina Batlle, Marc Fatar, Saskia Grudzenski, Joan Montaner, Mar Hernández-Guillamon
• E-Jahr: 2017
• Jahr: December 2017
• Umfang: 13 S.
• Fussnoten: Gesehen am 16.05.2018
• Titel Quelle: Enthalten in: Neurobiology of aging
• Ort Quelle: Amsterdam [u.a.] : Elsevier Science, 1980
• Jahr Quelle: 2017
• Band/Heft Quelle: 60(2017), Seite 116-128
• ISSN Quelle: 1558-1497
• DOI: doi:10.1016/j.neurobiolaging.2017.08.028
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Alzheimer's disease
• Sach-SW: ApoA-I
• Sach-SW: ApoA-I-Milano
• Sach-SW: APP23
• Sach-SW: Beta amyloid
• Sach-SW: Neuroinflammation
• K10plus-PPN: 1575187248

Abstract

Beyond the crucial role of apolipoprotein A-I (ApoA-I) on peripheral cholesterol metabolism, this apolipoprotein has also been implicated in beta amyloid (Aβ)-related neuropathologies. ApoA-I-Milano (M) is a mutated variant, which showed increased vasoprotective properties compared to ApoA-I-wild type in models of atherosclerosis and cardiovascular damage. We speculated that ApoA-I-M may also protect Aβ-affected vasculature and reverse some of the pathological features associated with Alzheimer's disease (AD). For this purpose, we produced and characterized human recombinant ApoA-I-wild type and ApoA-I-M proteins. Both of them were able to avoid the aggregation of Aβ in vitro, even though recombinant ApoA-I-M was significantly more effective in protecting endothelial cells from Aβ(1-42)-toxicity. Next, we determined the effect of chronic intravenous administration of rApoA-I-M in the APP23-transgenic mouse model of AD. We found reduced cerebral Aβ levels in mice that received rApoA-I-M, which were accompanied by a lower expression of astrocyte and microglia neuroinflammatory markers. Our results suggest an applicability of this molecule as a therapeutic candidate for protecting the brain in AD.