Cover Image

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

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 ty...

Full description

Saved in:
Bibliographic Details
Main Authors: Fernández de Retana Alda, Sofía (Author) , Fatar, Marc (Author) , Grudzenski-Theis, Saskia (Author)
Format: Article (Journal)
Language:English
Published: December 2017
In: Neurobiology of aging
Year: 2017, Volume: 60, Pages: 116-128
ISSN:1558-1497
DOI:10.1016/j.neurobiolaging.2017.08.028
Online Access:Verlag, Volltext: http://dx.doi.org/10.1016/j.neurobiolaging.2017.08.028
Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S0197458017302841
Get full text
Author Notes:Sofía Fernández-de Retana, Alex Montañola, Paula Marazuela, Maialen De La Cuesta, Aina Batlle, Marc Fatar, Saskia Grudzenski, Joan Montaner, Mar Hernández-Guillamon
Description
Summary: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.
Item Description:Gesehen am 16.05.2018
Physical Description:Online Resource
ISSN:1558-1497
DOI:10.1016/j.neurobiolaging.2017.08.028

Similar Items