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Donepezil effects on cholesterol and oxysterol plasma levels of Alzheimer’s disease patients

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Abstract

Cholesterol is an essential component in the structure and function of cell membranes and has been associated with the major pathological signatures of Alzheimer’s disease (AD). To maintain brain cholesterol homeostasis, it is converted into 24(S)-hydroxycholesterol (24OHC) which can be driven through the blood–brain barrier. Several studies have already described a decrease in 24OHC and an increase of 27(S)-hydroxycholesterol (27OHC) in AD, as a reflection of disease burden, the loss of metabolically active neurons and the degree of structural atrophy. It is also well known that peripheral cholesterol is altered in AD patients. However, there are no data regarding effects of AD treatment in this cholesterol pathway. Since a study from our group indicated a significant increase in membrane phospholipid metabolism by donepezil, the aim of this study was to evaluate the effect of short- and long-term donepezil treatment on cholesterol and metabolites 24OHC and 27OHC in plasma of AD patients and in healthy volunteers. At baseline, we found a decrease of 24OHC (p = 0.003) in AD patients. Cholesterol levels increased with donepezil treatment (p = 0.04) but no differences were observed regarding 24OHC and 27OHC. However, these results confirm and extend previous studies demonstrating disturbed cholesterol turnover in Alzheimer’s disease.

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Acknowledgements

The authors wish to gratefully acknowledge the contribution of Associação Beneficente Alzira Denise Hertzog da Silva (ABADHS) and NAPNA (Núcleo de Apoio à Pesquisa em Neurociências Aplicada—USP).

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  1. Alana C. Costa and Helena P. G. Joaquim contributed equally to this work.

Authors and Affiliations

  1. Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, University of Sao Paulo, Rua Dr. Ovídio Pires de Campos, 785, 3º andar, São Paulo, SP, 05403-010, Brazil

    Alana C. Costa, Helena P. G. Joaquim, Daniel S. Kerr, Orestes V. Forlenza, Wagner F. Gattaz & Leda Leme Talib

  2. Lipids Laboratory (LIM10), Faculty of Medical Sciences of the University of Sao Paulo, São Paulo, Brazil

    Valéria S. Nunes & Guilherme S. Ferreira

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  1. Alana C. Costa
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Contributions

Authors LLT and WFG designed the study. Author OVF performed patient recruitment and neuropsychiatry and clinical evaluation. Authors HPGJ, ACC and LLT managed the literature searches, wrote the first draft of the manuscript and undertook the statistical analysis. Authors VNS and ACC wrote the protocol and performed the laboratory analyses. All authors contributed to and have approved the final manuscript.

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Correspondence to Leda Leme Talib.

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Costa, A.C., Joaquim, H.P.G., Nunes, V.S. et al. Donepezil effects on cholesterol and oxysterol plasma levels of Alzheimer’s disease patients. Eur Arch Psychiatry Clin Neurosci 268, 501–507 (2018). https://doi.org/10.1007/s00406-017-0838-2

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