title: Cholesterol and amyloid-β: evidence for a cross-talk between astrocytes and neuronal cells.
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 Aβ(42) 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.
authors.affiliation: Department of Experimental Medicine, University of Genoa, Genoa, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Canepa
authors.forename: Roberta
authors.initials: R
authors.lastname: Borghi
authors.forename: Jose
authors.initials: J
authors.lastname: Viña
authors.forename: Nicola
authors.initials: N
authors.lastname: Traverso
authors.forename: Juan
authors.initials: J
authors.lastname: Gambini
authors.forename: Cinzia
authors.initials: C
authors.lastname: Domenicotti
authors.forename: Umberto M
authors.initials: UM
authors.lastname: Marinari
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Poli
authors.forename: Maria A
authors.initials: MA
authors.lastname: Pronzato
authors.forename: Roberta
authors.initials: R
authors.lastname: Ricciarelli
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000544:Alzheimer Disease / Q000378:metabolism / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D015153:Blotting, Western; D001923:Brain Chemistry; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D018920:Coculture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D006706:Homeostasis; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism*; D020239:Receptor Cross-Talk / Q000502:physiology
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D016229:Amyloid beta-Peptides; D002784:Cholesterol