Alzheimer disease (AD) is an age-related neurodegenerative disorder characterized by progressive memory loss, inability to perform the activities of daily living and personality changes. Unfortunately, drugs effective for this disease are limited to acetylcholinesterase inhibitors that do not impact disease pathogenesis. Statins, which belong to the class of cholesterol-reducing drugs, were proposed as novel agents useful in AD therapy, but the mechanism underlying their neuroprotective effect is still unknown. In this study, we show that atorvastatin may have antioxidant effects, in aged beagles, that represent a natural higher mammalian model of AD. Atorvastatin (80 mg/day for 14.5 months) significantly reduced lipoperoxidation, protein oxidation and nitration, and increased GSH levels in parietal cortex of aged beagles. This effect was specific for brain because it was not paralleled by a concomitant reduction in all these parameters in serum. In addition, atorvastatin slightly reduced the formation of cholesterol oxidation products in cortex but increased the 7-ketocholesterol/total cholesterol ratio in serum. We also found that increased oxidative damage in the parietal cortex was associated with poorer learning (visual discrimination task). Thus, a novel pharmacological effect of atorvastatin mediated by reducing oxidative damage may be one mechanism underlying benefits of this drug in AD.
|Number of pages||9|
|State||Published - Mar 2011|
Bibliographical noteFunding Information:
This work was supported by Alzheimer's Association [IIRG 03-5673 to EH and MPM] and NIH grant to D.A.B. [AG-05119]. E.B. is a Ph.D. student of the Catholic University of the Sacred Heart in Rome and was awarded a Fellowship from the Italian Society of Pharmacology.
- Alzheimer disease
- Cholesterol oxidation products
- Cognitive function
- Oxidative stress
ASJC Scopus subject areas