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

Publication date: Available online 5 September 2017
Source:Neurobiology of Aging
Author(s): Sofía Fernández-de Retana, Alex Montañola, Paula Marazuela, Maialen De La Cuesta, Aina Batlle, Marc Fatar, Saskia Grudzenski, Joan Montaner, Mar Hernández-Guillamon
Beyond the crucial role of apolipoproteinA-I (ApoA-I) on peripheral cholesterol metabolism, this apolipoprotein has also been implicated in β-amyloid (Aβ)-related neuropathologies. ApoA-I-Milano (M) is a mutated variant, which has been shown to present increased vasoprotective properties compared to ApoA-I-wild type (wt) 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-wt and ApoA-I-M proteins. Both of them were able to avoid the aggregation of Aβ in vitro, even though rApoA-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 levels of Aβ(1-40) and Aβ(1-42) 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.



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