Acetylcholinesterase inhibitors in Alzheimer's disease influence Zinc and Copper homeostasis

Research output: Contribution to journalArticle

Abstract

Background: Alzheimer's disease (AD) is the most common age-related neurodegenerative disease. An altered homeostasis of Zinc (Zn) and Copper (Cu), as well as a dysregulated expression of Zn-regulatory proteins have been previously described in AD. Acetylcholinesterase inhibitors (AChEI) are commonly used as AD treatment to improve cognitive function, but their effect on Zn homeostasis is still unexplored. Objectives: The aims of this study were to define the metal dyshomeostasis in AD patients, to investigate AChEI influence on Zn homeostasis and inflammation, and to analyze the relationship between cognitive impairment at two-year follow-up and metal concentrations, considering AChEI use. Methods and Results: 84 Healthy Elderly (HE) and 95 AD patients were enrolled (62 AchEI user and 33 AchEI naïve). HE showed similar plasma Zn and Cu concentrations and Cu/Zn ratio in comparison to AChEI users, but significantly higher Zn level, as well as lower Cu amount and Cu/Zn ratio than AChEI naïve patients. Moreover, AChEI users had increased Zn plasma level, reduced Cu amount, Cu/Zn ratio, and IL1β concentration and lower Zip2 lymphocytic expression vs. naïve patients. A multiple linear regression analysis showed that the MMSE score decline after two-year follow-up was reduced by AChEI therapy and was positively associated with plasma Zn decrease over time. Conclusion: Our data revealed that AChEI use may affect peripheral Zn and Cu homeostasis in AD patients, decrease Cu/Zn ratio demonstrating a general reduction of inflammatory status in patients under AChEI treatment. Finally, AChEI influence on circulating Zn could be implicated in the drug-related slowdown of cognitive decline.

Original languageEnglish
Pages (from-to)58-63
Number of pages6
JournalJournal of Trace Elements in Medicine and Biology
Volume55
DOIs
Publication statusPublished - Sep 1 2019

Fingerprint

Cholinesterase Inhibitors
Zinc
Copper
Alzheimer Disease
Homeostasis
Plasmas
Metals
Neurodegenerative diseases
Linear regression
Regression analysis
Neurodegenerative Diseases
Cognition
Linear Models
Therapeutics

Keywords

  • Acetylcholinesterase inhibitors
  • Alzheimer's disease
  • Copper
  • Inflammation
  • Zinc homeostasis
  • Zip2

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Inorganic Chemistry

Cite this

@article{4895145eb5644740af9ff8ed5971810a,
title = "Acetylcholinesterase inhibitors in Alzheimer's disease influence Zinc and Copper homeostasis",
abstract = "Background: Alzheimer's disease (AD) is the most common age-related neurodegenerative disease. An altered homeostasis of Zinc (Zn) and Copper (Cu), as well as a dysregulated expression of Zn-regulatory proteins have been previously described in AD. Acetylcholinesterase inhibitors (AChEI) are commonly used as AD treatment to improve cognitive function, but their effect on Zn homeostasis is still unexplored. Objectives: The aims of this study were to define the metal dyshomeostasis in AD patients, to investigate AChEI influence on Zn homeostasis and inflammation, and to analyze the relationship between cognitive impairment at two-year follow-up and metal concentrations, considering AChEI use. Methods and Results: 84 Healthy Elderly (HE) and 95 AD patients were enrolled (62 AchEI user and 33 AchEI na{\"i}ve). HE showed similar plasma Zn and Cu concentrations and Cu/Zn ratio in comparison to AChEI users, but significantly higher Zn level, as well as lower Cu amount and Cu/Zn ratio than AChEI na{\"i}ve patients. Moreover, AChEI users had increased Zn plasma level, reduced Cu amount, Cu/Zn ratio, and IL1β concentration and lower Zip2 lymphocytic expression vs. na{\"i}ve patients. A multiple linear regression analysis showed that the MMSE score decline after two-year follow-up was reduced by AChEI therapy and was positively associated with plasma Zn decrease over time. Conclusion: Our data revealed that AChEI use may affect peripheral Zn and Cu homeostasis in AD patients, decrease Cu/Zn ratio demonstrating a general reduction of inflammatory status in patients under AChEI treatment. Finally, AChEI influence on circulating Zn could be implicated in the drug-related slowdown of cognitive decline.",
keywords = "Acetylcholinesterase inhibitors, Alzheimer's disease, Copper, Inflammation, Zinc homeostasis, Zip2",
author = "R. Giacconi and C. Giuli and T. Casoli and M. Balietti and L. Costarelli and M. Provinciali and A. Basso and F. Piacenza and D. Postacchini and R. Galeazzi and P. Fattoretti and L. Nisi and P. Fabbietti and R. Papa and M. Malavolta",
year = "2019",
month = "9",
day = "1",
doi = "10.1016/j.jtemb.2019.06.001",
language = "English",
volume = "55",
pages = "58--63",
journal = "Journal of Trace Elements in Medicine and Biology",
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publisher = "Urban und Fischer Verlag GmbH und Co. KG",

}

TY - JOUR

T1 - Acetylcholinesterase inhibitors in Alzheimer's disease influence Zinc and Copper homeostasis

AU - Giacconi, R.

AU - Giuli, C.

AU - Casoli, T.

AU - Balietti, M.

AU - Costarelli, L.

AU - Provinciali, M.

AU - Basso, A.

AU - Piacenza, F.

AU - Postacchini, D.

AU - Galeazzi, R.

AU - Fattoretti, P.

AU - Nisi, L.

AU - Fabbietti, P.

AU - Papa, R.

AU - Malavolta, M.

PY - 2019/9/1

Y1 - 2019/9/1

N2 - Background: Alzheimer's disease (AD) is the most common age-related neurodegenerative disease. An altered homeostasis of Zinc (Zn) and Copper (Cu), as well as a dysregulated expression of Zn-regulatory proteins have been previously described in AD. Acetylcholinesterase inhibitors (AChEI) are commonly used as AD treatment to improve cognitive function, but their effect on Zn homeostasis is still unexplored. Objectives: The aims of this study were to define the metal dyshomeostasis in AD patients, to investigate AChEI influence on Zn homeostasis and inflammation, and to analyze the relationship between cognitive impairment at two-year follow-up and metal concentrations, considering AChEI use. Methods and Results: 84 Healthy Elderly (HE) and 95 AD patients were enrolled (62 AchEI user and 33 AchEI naïve). HE showed similar plasma Zn and Cu concentrations and Cu/Zn ratio in comparison to AChEI users, but significantly higher Zn level, as well as lower Cu amount and Cu/Zn ratio than AChEI naïve patients. Moreover, AChEI users had increased Zn plasma level, reduced Cu amount, Cu/Zn ratio, and IL1β concentration and lower Zip2 lymphocytic expression vs. naïve patients. A multiple linear regression analysis showed that the MMSE score decline after two-year follow-up was reduced by AChEI therapy and was positively associated with plasma Zn decrease over time. Conclusion: Our data revealed that AChEI use may affect peripheral Zn and Cu homeostasis in AD patients, decrease Cu/Zn ratio demonstrating a general reduction of inflammatory status in patients under AChEI treatment. Finally, AChEI influence on circulating Zn could be implicated in the drug-related slowdown of cognitive decline.

AB - Background: Alzheimer's disease (AD) is the most common age-related neurodegenerative disease. An altered homeostasis of Zinc (Zn) and Copper (Cu), as well as a dysregulated expression of Zn-regulatory proteins have been previously described in AD. Acetylcholinesterase inhibitors (AChEI) are commonly used as AD treatment to improve cognitive function, but their effect on Zn homeostasis is still unexplored. Objectives: The aims of this study were to define the metal dyshomeostasis in AD patients, to investigate AChEI influence on Zn homeostasis and inflammation, and to analyze the relationship between cognitive impairment at two-year follow-up and metal concentrations, considering AChEI use. Methods and Results: 84 Healthy Elderly (HE) and 95 AD patients were enrolled (62 AchEI user and 33 AchEI naïve). HE showed similar plasma Zn and Cu concentrations and Cu/Zn ratio in comparison to AChEI users, but significantly higher Zn level, as well as lower Cu amount and Cu/Zn ratio than AChEI naïve patients. Moreover, AChEI users had increased Zn plasma level, reduced Cu amount, Cu/Zn ratio, and IL1β concentration and lower Zip2 lymphocytic expression vs. naïve patients. A multiple linear regression analysis showed that the MMSE score decline after two-year follow-up was reduced by AChEI therapy and was positively associated with plasma Zn decrease over time. Conclusion: Our data revealed that AChEI use may affect peripheral Zn and Cu homeostasis in AD patients, decrease Cu/Zn ratio demonstrating a general reduction of inflammatory status in patients under AChEI treatment. Finally, AChEI influence on circulating Zn could be implicated in the drug-related slowdown of cognitive decline.

KW - Acetylcholinesterase inhibitors

KW - Alzheimer's disease

KW - Copper

KW - Inflammation

KW - Zinc homeostasis

KW - Zip2

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U2 - 10.1016/j.jtemb.2019.06.001

DO - 10.1016/j.jtemb.2019.06.001

M3 - Article

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VL - 55

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JO - Journal of Trace Elements in Medicine and Biology

JF - Journal of Trace Elements in Medicine and Biology

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