Despite the large availability of data regarding the mechanisms at the basis of β-
amyloid production in Alzheimer’s disease (AD), the factors responsible for β-amyloid
accumulation in neurons of AD patients until now have not been entirely clarified. Several
metal ions have been indicated as possible triggers of the main conformational
modifications of β-amyloid protein, and metal homeostasis disarrangement has been
proposed as a relevant pathological cofactor of neurodegeneration. Epidemiological
evidences suggest a possible association between exposure to increased amounts of
multiple metals and onset and progression of AD. According to this hypothesis, metals
could induce oxidative stress in neurons, developing neurodegenerative disease. In this
chapter, the role of various trace metals as cofactors of a poor cognitive function and of an
increased risk of dementia leading to AD will be discussed. In particular, this study is
aimed to critically analyze the role played by copper, iron, zinc and aluminium in
neurodegeneration. Based on the current evidences concerning the relationship between
these metal ions and onset and progression of AD, no definitive recommendations are, at
the best of our knowledge, possible. However, foods rich in metals such as iron and copper
should be discouraged, as well as caution should be suggested in exposure to aluminium
sources. Further studies on the relationship between metal overexposure and AD
development hopefully will open new opportunities for the prevention and management of
neurodegenerative diseases.
Keywords: Alzheimer’s disease, neurodegenerative diseases, β-amyloid protein,
oxidative stress, copper, iron, zinc, aluminium.