Ceruloplasmin and iron in Alzheimer’s disease and Parkinson’s disease: a synopsis of recent studies

Abstract

Jakob Kristinsson,1 Jón Snaedal,2 Gudlaug Tórsdóttir,1,2 Torkell Jóhannesson11Department of Pharmacology and Toxicology, University of Iceland, Reykjavik, Iceland; 2Department of Geriatrics, Landspitali University Hospital, Reykjavik, IcelandAbstract: Ceruloplasmin (Cp) concentration and oxidative activity in serum are lowered in Parkinson’s disease (PD). In most PD patients, iron increases in the substantia nigra in the midbrain. In PD, the low Cp concentration and activity in serum and the high iron amounts in the substantia nigra appears to be correlated. An hereditary background is common in PD and variations in the Cp gene that have been found in PD are associated with high iron levels in the substantia nigra. Variations in Cp synthesis and in the incorporation of copper into the Cp molecule are essential features of PD. In Alzheimer’s disease (AD), the Cp activity in serum is lowered but not the concentration, except in the advanced stages of the disease. Generally, iron is not increased in the AD brain. In the AD brain, iron accumulates in neuritic plaques and in neurofibrillary tangles. There is also increased risk of iron-mediated tissue damage, which may possibly be counteracted by Cp. At the same time, the AD brain is short in copper, which presumably results in the deficient activity of many copper enzymes in the brain, in addition to Cp. Lowered Cp activity in serum most likely stems from lessened incorporation of copper in the Cp molecule and similar incorporation defects might also apply to other copper enzymes in AD.Keywords: ceruloplasmin, iron, copper, Alzheimer´s disease, Parkinson´s disease