Copper phenotype in Alzheimer's disease: dissecting the pathway.

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 independent 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 progression. Specifically, different authors have hypothesized that alterations in metal metabolism are associated with an increased in metal-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.