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Am J Neurodegener Dis 2013;2(2):46-56
Review Article
Copper phenotype in Alzheimer’s disease: dissecting the pathway
Rosanna Squitti, Renato Polimanti
Department of Neuroscience, AFaR - “San Giovanni Calibita” Fatebenefratelli Hospital, Rome, Italy; Laboratorio di
Neurodegenerazione, IRCCS San Raffaele Pisana, Italy; Department of Biology, University of Rome “Tor Vergata”,
Rome, Italy
Received May 13, 2013; Accepted May 31, 2013; Epub June 21, 2013; Published July 1, 2013
Abstract: Alzheimer’s disease (AD) is the most common form of dementia. Several hypotheses have been put forward
to explain the basis of disease onset and progression. Unfortunately, none of these seems to clarify the complexity of
the pathogenesis. In fact, diverse and inde-pendent pathogenetic pathways can be disrupted at the same time, and
each contributes to disease etiology. In recent years, researchers have begun studying biometals more deeply. A
number of studies have shown that metal dyshomeostasis may enhance AD onset and pro-gression. Specifically,
different authors have hypothesized that alterations in metal metabolism are associated with an increased in met-al-
related oxidative stress and beta-amyloid oligomer formation and precipitation. Studies conducted in vivo, in vitro, in
living patients and in silico studies have demonstrated that local and systemic defects in copper metabolism are
characteristic signs of AD. This strongly supports the hypothesis that copper pathways may be disrupted by the
disease. More specifically, a copper phenotype can be proposed for AD, based on defects found in genes involved in
copper metabolism. In this review, we describe copper dyshomeostasis in AD patients and attempt to explain the
basis of the AD copper phenotype. Dissecting copper pathways, we highlight mechanisms which may be at the basis
of the disease. We also discuss various associated translation outcomes. (AJND1305004).
Keywords: Alzheimer’s disease, copper, metals, neurodegeneration, etiology, pathogenesis, systems biology,
diagnosis, drugs, Wilson’s dis-ease
Address correspondence to: Dr. Rosanna Squitti, Department of Neuroscience, AFaR - Ospedale Fatebenefratelli,
00186, Rome, Italy. Tel: +39 06 6837 385; Fax: +39 06 6837 300; E-mail: rosanna.squitti@afar.it
Review Article
Copper phenotype in Alzheimer’s disease: dissecting the pathway
Rosanna Squitti, Renato Polimanti
Department of Neuroscience, AFaR - “San Giovanni Calibita” Fatebenefratelli Hospital, Rome, Italy; Laboratorio di
Neurodegenerazione, IRCCS San Raffaele Pisana, Italy; Department of Biology, University of Rome “Tor Vergata”,
Rome, Italy
Received May 13, 2013; Accepted May 31, 2013; Epub June 21, 2013; Published July 1, 2013
Abstract: Alzheimer’s disease (AD) is the most common form of dementia. Several hypotheses have been put forward
to explain the basis of disease onset and progression. Unfortunately, none of these seems to clarify the complexity of
the pathogenesis. In fact, diverse and inde-pendent pathogenetic pathways can be disrupted at the same time, and
each contributes to disease etiology. In recent years, researchers have begun studying biometals more deeply. A
number of studies have shown that metal dyshomeostasis may enhance AD onset and pro-gression. Specifically,
different authors have hypothesized that alterations in metal metabolism are associated with an increased in met-al-
related oxidative stress and beta-amyloid oligomer formation and precipitation. Studies conducted in vivo, in vitro, in
living patients and in silico studies have demonstrated that local and systemic defects in copper metabolism are
characteristic signs of AD. This strongly supports the hypothesis that copper pathways may be disrupted by the
disease. More specifically, a copper phenotype can be proposed for AD, based on defects found in genes involved in
copper metabolism. In this review, we describe copper dyshomeostasis in AD patients and attempt to explain the
basis of the AD copper phenotype. Dissecting copper pathways, we highlight mechanisms which may be at the basis
of the disease. We also discuss various associated translation outcomes. (AJND1305004).
Keywords: Alzheimer’s disease, copper, metals, neurodegeneration, etiology, pathogenesis, systems biology,
diagnosis, drugs, Wilson’s dis-ease
Address correspondence to: Dr. Rosanna Squitti, Department of Neuroscience, AFaR - Ospedale Fatebenefratelli,
00186, Rome, Italy. Tel: +39 06 6837 385; Fax: +39 06 6837 300; E-mail: rosanna.squitti@afar.it