Donepezil (DNPZ), an acetyl-cholinesterase inhibitor (AChEI), is widely used as a symptomatic drug in AD, given the involvement of cholinergic damage in the onset of memory loss. DNPZ, besides being able to improve acetylcholine (ACh) transmission, might have a neuroprotective effect reducing toxic Abeta fibrils and regulating the immune response. Considering that we previously showed a specific increase of plasma anti-Abeta1–42 antibodies in AD patients treated with AChEI, we evaluated in this study the role of DNPZ in favouring a Th2 phenotype, involved in modulating the immune humoral response. Moreover we hypothesized that this mechanism might be mediated by the a7-nicotinic ACh receptor expressed in lymphocytes. 60 patients with mild or moderate AD, either treated (n=22) or not (n=38) with DNPZ, and 30 controls were enrolled. AD DNPZ+ showed significantly higher plasma levels of anti-Abeta antibodies than DNPZ− (+40%) and lower levels of Abeta 1–42 than controls (−50%). In a subgroup of subjects, GATA-3, a transcription factor involved in Th2 differentiation, and a7nAChR expression was evaluated. No differences were found in GATA-3 mRNA in AD DNPZ+ when compared to DNPZ− and controls. On the opposite, we found by chromatine immunoprecipitation a significant three-fold increase of the association of GATA-3 with the IL-5-promoter in DNPZ+ patients, which also showed a significant twofold increase in a7-nAChR mRNA, with respect to DNPZ-ones. In vitro analyses demonstrated that the capacity of DNPZ to modulate GATA-3 expression is mediated by a7nAChR, since MLA, a specific antagonist, prevents it. Further studies are needed to better understand the role of DNPZ in modulating the immune response against Abeta, possibly ameliorating therapeutic strategies for AD

Tremolizzo, L., Conti, E., Santarone, M., Tironi, M., Zoia, C., Appollonio, I., et al. (2013). Donepezil modulates the endogenous immune response in Alzheimer’s disease, an ex vivo and in vitro study. In Abstract VIII Congresso Nazionale Sindem 2013 (pp.36-36).

Donepezil modulates the endogenous immune response in Alzheimer’s disease, an ex vivo and in vitro study

TREMOLIZZO, LUCIO
Primo
;
CONTI, ELISA
Secondo
;
ZOIA, CHIARA PAOLA;APPOLLONIO, ILDEBRANDO
Penultimo
;
FERRARESE, CARLO
Ultimo
2013

Abstract

Donepezil (DNPZ), an acetyl-cholinesterase inhibitor (AChEI), is widely used as a symptomatic drug in AD, given the involvement of cholinergic damage in the onset of memory loss. DNPZ, besides being able to improve acetylcholine (ACh) transmission, might have a neuroprotective effect reducing toxic Abeta fibrils and regulating the immune response. Considering that we previously showed a specific increase of plasma anti-Abeta1–42 antibodies in AD patients treated with AChEI, we evaluated in this study the role of DNPZ in favouring a Th2 phenotype, involved in modulating the immune humoral response. Moreover we hypothesized that this mechanism might be mediated by the a7-nicotinic ACh receptor expressed in lymphocytes. 60 patients with mild or moderate AD, either treated (n=22) or not (n=38) with DNPZ, and 30 controls were enrolled. AD DNPZ+ showed significantly higher plasma levels of anti-Abeta antibodies than DNPZ− (+40%) and lower levels of Abeta 1–42 than controls (−50%). In a subgroup of subjects, GATA-3, a transcription factor involved in Th2 differentiation, and a7nAChR expression was evaluated. No differences were found in GATA-3 mRNA in AD DNPZ+ when compared to DNPZ− and controls. On the opposite, we found by chromatine immunoprecipitation a significant three-fold increase of the association of GATA-3 with the IL-5-promoter in DNPZ+ patients, which also showed a significant twofold increase in a7-nAChR mRNA, with respect to DNPZ-ones. In vitro analyses demonstrated that the capacity of DNPZ to modulate GATA-3 expression is mediated by a7nAChR, since MLA, a specific antagonist, prevents it. Further studies are needed to better understand the role of DNPZ in modulating the immune response against Abeta, possibly ameliorating therapeutic strategies for AD
abstract + poster
Donepezil, immune response, abeta
English
Congresso SINDEM
2013
Abstract VIII Congresso Nazionale Sindem 2013
2013
28
suppl 1
36
36
none
Tremolizzo, L., Conti, E., Santarone, M., Tironi, M., Zoia, C., Appollonio, I., et al. (2013). Donepezil modulates the endogenous immune response in Alzheimer’s disease, an ex vivo and in vitro study. In Abstract VIII Congresso Nazionale Sindem 2013 (pp.36-36).
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/141116
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