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FOXO1 locus and acetylcholinesterase inhibitors in elderly patients with Alzheimer’s disease

Authors Paroni G, Seripa D, Fontana A, D'Onofrio G, Gravina C, Urbano M, Cascavilla L, Pellegrini F, Greco A, Pilotto A

Received 25 March 2014

Accepted for publication 30 June 2014

Published 21 October 2014 Volume 2014:9 Pages 1783—1791

DOI https://doi.org/10.2147/CIA.S64758

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Giulia Paroni,1 Davide Seripa,1 Andrea Fontana,2 Grazia D’Onofrio,1 Carolina Gravina,1 Maria Urbano,1 Leandro Cascavilla,2 Fabio Pellegrini,2,3 Antonio Greco,1 Alberto Pilotto1,4

1Gerontology and Geriatrics Research Laboratory, 2Unit of Biostatistics, 3Unit of Biostatistics, Fondazione Mario Negri Sud, Santa Maria Imbaro (CH), Italy; 4Geriatrics Unit, Azienda ULSS 16 Padova, San Antonio Hospital, Padova, Italy

Objective: Acetylcholinesterase inhibitors (AChEIs) may reduce the oxidative stress in brain of Alzheimer’s disease (AD) patients. Forkhead box O1 (FoxO1) protein has been reported as the link between oxidative stress and AD. We evaluated a potential association between FOXO1 gene locus and the response to AChEI treatment in patients with sporadic AD.
Methods: In this prospective study, 109 Caucasian AD patients were treated with standard doses of donepezil, galantamine, or rivastigmine for 6 months. Functional and cognitive status were evaluated at baseline and after treatment. Response to therapy was defined according to the National Institute for Health and Clinical Excellence criteria. Genotype analyses, including the APOE polymorphism, were made in blinded fashion.
Results: A significantly higher frequency of FOXO1 rs7981045 G/G genotype was observed in nonresponders compared with responders (17.14% versus 2.70%, P=0.010). Age, sex, and APOE-adjusted logistic regression analysis confirmed that patients with the G/G genotype had a significantly higher risk of poor response to AChEI treatment (odds ratio =10.310; 95% confidence interval, 1.510–70.362). Haplotype analysis revealed significant differences in haplotype frequency distribution between these groups.
Conclusion: FOXO1 may influence the clinical response to AChEIs in AD patients.

Keywords: forkhead box O1, acetylcholinesterase inhibitors, response to treatment

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