Copper in Alzheimer’s Disease

Alzheimer’s disease (AD) is the most common form of dementia. Several brain alterations, such as loss of neurons, accumulation of beta amyloid (Aβ), and neurofibrillary tangles have been long associated with this disease. More recently, also an imbalance of metal levels and a high burden of oxidative stress have been recognized as contributors. A number of meta-analyses and systemic reviews point at the breakdown of copper homeostasis as a causative factor of both Mild Cognitive Impairment (MCI) and AD, manifesting itself with general reduction of copper in the brain, an increase in the blood, and an increase in the serum of the small fraction of copper which does not bind to ceruloplasmin. The latter is redox active and thus potentially neurotoxic, as it is able to cross the blood brain barrier (BBB) and produce oxidative stress by interacting with Aβ and Tau proteins. This chapter describes how this copper status contributes to define a copper ‘subtype’ of AD, a notion which has been receiving much credit in the last few years.