Affiliations: Institute of Pathology, Case Western Reserve University, Cleveland, Ohio USA | Institut für Biochemie und Molekularbiologie I, Heinrich-Heine-Universität Düsseldorf, Universitätsstr. 1, D-40225 Düsseldorf, Germany Tel.: +49 211 811 5358; Fax: +49 211 811 3029; E-mail: polidori@uni-duesseldorf.de
Correspondence:
[*]
Corresponding author: Gemma Casadesus, Ph.D., Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, Ohio 44106, USA. Tel.: +1 216 368 6708; Fax: +1 216 368 8964; E-mail: gxc40@case.edu.
Abstract: Free radical formation, abnormalities in iron and copper distribution, and metal-catalyzed oxidation have all been noted in Alzheimer disease and are thought to play an important role in disease pathogenesis. Metal-catalyzed hydroxyl radical formation results in damage to every category of macromolecule found in the vulnerable neuronal populations in Alzheimer disease. In fact, redox activity resides within the cytosol of vulnerable neurons. Since oxidative damage represents one of the earliest pathological changes in Alzheimer disease, it is likely that aberrant redox activity is among the earliest changes in the transition to the disease state. In this review, we consider the wealth of evidence implicating a central role for metals in Alzheimer disease.
