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Altered cholesterol ester cycle in ex vivo skin fibroblasts from Alzheimer patients

Alessandra Pani¹, Sandra Dessi¹, Giacomo Diaz², Claudia Abete¹, Claudia Mulas¹, Claudia Norfo ¹, Marirosa Putzolu¹, Maria Dolores Cannas¹, Christina Doriana Orru¹, Alessandra Mocali³, Pier Luigi Cocco³, Paolo La Colla¹ & Francesco Paoletti⁴

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1. University of Cagliari, Biomedical Science & Technology
2. University of Cagliari, Department of Cytomorphology
3. University of Florence, Experimental Pathology and Oncology
4. University of Florence, Experimental Pathology and Oncology

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Document Type:

Manuscript

Date:

Received 18 February 2008 17:15 UTC; Posted 19 February 2008

Subjects:

Molecular Cell Biology, Neuroscience

Tags:

• Cholesterol ester cycle
• Alzheimer
• s
• disease"

Abstract:

Recent studies in both animal and cell models of Alzheimer’s disease (AD) indicated that sub-cellular cholesterol distribution seems to regulate amyloid-beta (Aβ) generation in the brain. In particular, cholesterol-esters (CE), rather than total cholesterol levels, appear directly correlated with Aβ production. Here we observed that, similarly to brain cells, skin fibroblasts obtained from AD patients produce and accumulate more CE than skin fibroblasts from age-matched healthy controls do. AD fibroblasts also exhibited a 2 fold increase in the expression of ACAT1, in addition to lower levels of SREBP2, nCEH, Caveolin-1 and ABCA1 mRNA levels, all of which are involved in the CE cycle. HMGCoA-reductase and LDL-receptor mRNAs levels did not show statistically significant changes in AD, compared to non-AD, cells. Furthermore, although APP mRNA did not significantly vary, neprilysin (NEP), the most important enzyme in the proteolysis of Aβ, was expressed at very low levels in skin fibroblasts of sporadic AD patients. Our results contribute to the concept that AD may be the consequence of a basic and systemic defect in the CE cycle. Moreover, our results identify new possible targets for the diagnosis, prevention, and cure or, at least, amelioration of the symptoms of AD.

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This document is licensed to the public under the Creative Commons Attribution 3.0 License

How to cite this document:

Pani, Alessandra, Dessi, Sandra, Diaz, Giacomo, Abete, Claudia, Mulas, Claudia, Norfo , Claudia, Putzolu, Marirosa, Cannas, Maria Dolores, Orru, Christina Doriana, Mocali, Alessandra, Cocco, Pier Luigi, La Colla, Paolo, and Paoletti, Francesco. Altered cholesterol ester cycle in ex vivo skin fibroblasts from Alzheimer patients. Available from Nature Precedings <http://hdl.handle.net/10101/npre.2008.1602.1> (2008)

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