Aluminium and iron, but neither copper nor zinc, are key to the precipitation of beta-sheets of Abeta_{42} in senile plaque cores in Alzheimer's disease.
A number of metals including Fe(II)/Fe(III), Al(III), Zn(II) and Cu(II) are found co-localised with beta-sheets of Abeta_{42} in senile plaque cores in AD brain. We know neither why nor how the co-localisation takes place or, indeed, if it is entirely aberrant or partly protective. There are data from in vitro studies which may begin to explain some of these unanswered questions and in considering these I have summised that Al(III) and Fe(III)/Fe(II) are directly involved in the precipitation of beta-sheets of Abeta_{42} in senile plaque cores whereas the presence of Cu(II) and Zn(II) is adventitious. The co-deposition of Al(III), Fe(III) and beta-sheets of Abeta_{42} could act as a source of reactive oxygen species and begin to explain some of the oxidative damage found in the immediate vicinity of senile plaques. Whether such metal-Abeta_{42} synergisms are an integral part of the aetiology of AD remains to be confirmed.
Exley
Christopher
C
Birchall Centre for Inorganic Chemistry and Materials Science, Keele University, Staffordshire, UK. c.exley@chem.keele.ac.uk
D000535:Aluminum / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D020134:Catalytic Domain / Q000502:physiology; D018929:Cell Culture Techniques; D003300:Copper / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D058225:Plaque, Amyloid / Q000378:metabolism*; D017433:Protein Structure, Secondary / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015032:Zinc / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C075222:amyloid beta-protein (1-42); D003300:Copper; D000535:Aluminum; D007501:Iron; D015032:Zinc