Elevated Manganese Levels in Blood and CNS Occur Prior to Onset of Clinical Signs in Scrapie and BSE

¹ Department of Biology and Biochemistry, University of Bath, Bath, BA2 7AY, UK
² Department of Chemistry, University of Hull, Hull HU6 7RX, UK
³ Division of Veterinary Biomedical Sciences, University of Edinburgh, Edinburgh, EH9 1QH, UK

^* To whom correspondence should be addressed. E-mail: bssdrb{at}bath.ac.uk.

	Abstract

Prion diseases or transmissible spongiform encephalopathies are neurodegenerative diseases that can only be accurately diagnosed by analysis of central nervous system tissue for the presence of an abnormal isoform of the prion protein known as PrP^Sc. Furthermore, these diseases have long incubation periods during which there are no clear symptoms but where the infectious agent could still be present in tissues. Therefore the development of diagnostic assays to detect a surrogate marker for the presence of prion disease is essential. Previous studies on mice experimentally infected with scrapie suggested that changes in the levels of manganese occur in both the blood and brain prior to the onset of symptoms of the disease. In order to assess whether these findings have relevance to the animal diseases scrapie and bovine spongiform encephalopathy (BSE), tissues from BSE and scrapie infected cattle and sheep were analysed for their metal content and compared to values for non infected animals. In both field cases and experimentally infected animals elevated manganese was associated with prion infection. Although some central nervous system regions showed elevated manganese other regions did not. The most consistent finding was elevation of manganese in blood. This change was present in experimentally infected animals before the onset of symptoms. In scrapie infected sheep, elevated manganese levels occurred regardless of the genotype of the sheep, and was even detected in scrapie resistant sheep where no symptoms of disease were detected. These findings suggest that elevated blood manganese could be a potential diagnostic marker for prion infection even in the absence of apparent clinical disease.

Key Words: scapie, prion, BSE, copper, metal

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				M. W. Brazier, P. Davies, E. Player, F. Marken, J. H. Viles, and D. R. Brown Manganese Binding to the Prion Protein J. Biol. Chem., May 9, 2008; 283(19): 12831 - 12839. [Abstract] [Full Text] [PDF]