Affiliations: [a] Department of Experimental Medicine, University of Genoa, Genoa, Italy | [b] Department of Neuroscience, Ophthalmology and Genetics, University of Genoa, Genoa, Italy | [c] Department of Physiology, University of Valencia, Valencia, Spain | [d] Department of Clinical and Biological Sciences, University of Turin, San Luigi Hospital, Turin, Italy
Correspondence:
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Correspondence to: Roberta Ricciarelli, Department of Experimental Medicine, Section of General Pathology, Via L.B. Alberti, 2, 16132 Genoa, Italy. Tel.: +39 010 3538831; Fax: +39 010 3538836; E-mail: [email protected].
Abstract: Accumulating data supports the concept that alterations of cholesterol metabolism might influence the development of Alzheimer's disease (AD), a neurodegenerative disorder characterized by progressive accumulation of amyloid-β (Aβ) peptides in the brain. Changes in the neuronal production of Aβ have been described as a function of cholesterol levels, thus suggesting a causal link between cholesterol homeostasis dysregulation and AD pathogenesis. Under physiological conditions, cholesterol uptake in the brain is efficiently prevented by the blood-brain barrier, and mature neurons are thought to rely on glial cells for their cholesterol supply. In the present study, we tested the hypothesis that Aβ may serve as a signaling molecule capable of informing the astroglial network about the neuronal need for cholesterol. Collectively, our data bolster this hypothesis and demonstrate, for the first time, that Aβ42 exerts an inhibitory effect on the expression of the cholesterol transporter ABCA1 in cultured astrocytes. Accordingly, we also show that ABCA1 expression is reduced in the brain of AβPP/PS1 transgenic mice. These results provide a biological function for Aβ peptides and may help to define the pathogenic relationship between cholesterol metabolism in brain and AD.
