Involvement of amyloid β precursor protein (AβPP) modulated copper homeostasis in Alzheimer's disease

Issue title: Dedicated to Prof. Marino Nicolini

Article type: Research Article

Authors: Bayer, Thomas A.^a | Multhaup, Gerd^b

Affiliations: [a] Universität des Saarlandes, Klinik für Psychiatrie, Abteilung für Neurobiologie, D-66421 Homburg, Germany. E-mail: thomas.bayer@uniklinik-saarland.de | [b] Freie Universität Berlin, Institut für Chemie/Biochemie, Thielallee 63, D-14195 Berlin, Germany. E-mail: multhaup@chemie.fu-berlin.de

Abstract: AβPP is involved in Cu homeostasis in mouse and man. In vitro observations and in vivo data obtained from AβPP mouse models at least provide strong evidence that AβPP and Aβ overproduction enables intracellular Cu to be transported out of the cell. The increased Cu efflux seems to lead to a Cu deficiency and a subsequently reduced SOD-1 activity. Studies have shown that a disturbed metal-ion homeostasis with elevated serum Cu levels occurs in Alzheimer and Down's patients and lowered levels in post-mortem AD brain. We conclude that bioavailable Cu has beneficial and specific effects in Alzheimer's disease transgenic mice, and suggest that our observation can be regarded as a proof-of-concept for a prophylactic approach to overcome the observed CNS Cu deficiency in the brain of Alzheimer's disease patients.

Keywords: AβPP, Alzheimer's disease, Cu deficiency, amyloid, pathology, transgenic model, SOD-1

DOI: 10.3233/JAD-2005-8212

Journal: Journal of Alzheimer's Disease, vol. 8, no. 2, pp. 201-206, 2005