Abstract
The notion that a copper dysfunction is implicated in Alzheimers disease (AD) is based on a number of observations from in vitro and clinical studies, as well as animal models. However, there is still significant controversy over whether it is an excess or a deficiency of copper to be involved in the pathogenesis of AD. Numerous studies support the hypothesis that an excess of copper contributes to AD, but experimental evidence in transgenic mouse models seems to suggest the contrary, and at least one clinical study shows that cognitive decline correlates positively with low copper levels. We have recently reported on a deregulation of the ceruloplasmin-copper relationship, specific to AD patients, consisting of an elevation of the copper pool not bound to ceruloplasmin, i.e. ‘free’ copper. This phenomenon could provide an explanation of the contrasting results obtained in clinical studies. Several clinical trials have been attempted in search of an anti-metal effect counteracting AD progression. Some of them have delivered encouraging results indicating that “metal protein attenuating compounds” can indeed alter positively the progression of the disease. This review summarizes these clinical studies and provides an overview of those in progress and in preparation.
Keywords: Copper, ceruloplasmin, Alzheimer disease, metal protein attenuating compounds, therapy, ‘free’ copper
Current Alzheimer Research
Title: Agents Complexing Copper as a Therapeutic Strategy for the Treatment of Alzheimers Disease
Volume: 6 Issue: 6
Author(s): Rosanna Squitti and Carlo Salustri
Affiliation:
Keywords: Copper, ceruloplasmin, Alzheimer disease, metal protein attenuating compounds, therapy, ‘free’ copper
Abstract: The notion that a copper dysfunction is implicated in Alzheimers disease (AD) is based on a number of observations from in vitro and clinical studies, as well as animal models. However, there is still significant controversy over whether it is an excess or a deficiency of copper to be involved in the pathogenesis of AD. Numerous studies support the hypothesis that an excess of copper contributes to AD, but experimental evidence in transgenic mouse models seems to suggest the contrary, and at least one clinical study shows that cognitive decline correlates positively with low copper levels. We have recently reported on a deregulation of the ceruloplasmin-copper relationship, specific to AD patients, consisting of an elevation of the copper pool not bound to ceruloplasmin, i.e. ‘free’ copper. This phenomenon could provide an explanation of the contrasting results obtained in clinical studies. Several clinical trials have been attempted in search of an anti-metal effect counteracting AD progression. Some of them have delivered encouraging results indicating that “metal protein attenuating compounds” can indeed alter positively the progression of the disease. This review summarizes these clinical studies and provides an overview of those in progress and in preparation.
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Cite this article as:
Squitti Rosanna and Salustri Carlo, Agents Complexing Copper as a Therapeutic Strategy for the Treatment of Alzheimers Disease, Current Alzheimer Research 2009; 6 (6) . https://dx.doi.org/10.2174/156720509790147133
DOI https://dx.doi.org/10.2174/156720509790147133 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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