| First Author | Fernández-de Retana S | Year | 2017 |
| Journal | Neurobiol Aging | Volume | 60 |
| Pages | 116-128 | PubMed ID | 28941727 |
| Mgi Jnum | J:258051 | Mgi Id | MGI:6116619 |
| Doi | 10.1016/j.neurobiolaging.2017.08.028 | Citation | Fernandez-de Retana S, et al. (2017) Intravenous treatment with human recombinant ApoA-I Milano reduces beta amyloid cerebral deposition in the APP23-transgenic mouse model of Alzheimer's disease. Neurobiol Aging 60:116-128 |
| abstractText | Beyond the crucial role of apolipoprotein A-I (ApoA-I) on peripheral cholesterol metabolism, this apolipoprotein has also been implicated in beta amyloid (Abeta)-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 Abeta-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 Abeta in vitro, even though recombinant ApoA-I-M was significantly more effective in protecting endothelial cells from Abeta(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 Abeta 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. |
