Journal
JOURNAL OF ALZHEIMERS DISEASE
Volume 25, Issue 4, Pages 645-653Publisher
IOS PRESS
DOI: 10.3233/JAD-2011-110053
Keywords
Alzheimer's disease; amyloid-beta protein precursor; ATP-binding cassette transporter A1; sterols
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Funding
- University of Genoa
- Italian Ministry of University and Research [2008N9N9KL_002]
- Spanish Ministry of Education and Science [SAF2008-00270]
- Red Tematica de investigacipn cooperativa en envejecimiento y fragilidad [ISCIII2006-RED13-027]
- EU [B35]
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Accumulating data support 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-beta (A beta) peptides in the brain. Changes in the neuronal production of A beta 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 A beta 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 A beta(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 A beta PP/PS1 transgenic mice. These results provide a biological function for A beta peptides and may help to define the pathogenic relationship between cholesterol metabolism in brain and AD.
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