Prion proteins (PrP(C)) are cell membrane glycoproteins that can be found in many cell types, but specially in neurons. Many studies have suggested PrP(C)'s participation in metal transport and cellular protection against stress in the central nervous system (CNS). On the other hand PrP(Sc), the misfolded isoform of PrP(C) and the pathogenic agent in transmissible spongiform encephalopathies (TSE), has been associated with brain metal dyshomeostasis in prion diseases. Thus, changes in metal concentration associated with protein misfolding and aggregation have been reported for human and animal prion diseases, as well as for other neurodegenerative disorders, such as Parkinson's and Alzheimer's disease. The use of metal concentrations in tissues as surrogate markers for early detection of TSEs has been suggested. Studies on the accumulation of metals in free-ranging white-tailed deer have not been conducted. This study established concentrations of copper, iron, manganese, and magnesium in 2 diagnostic tissues used for CWD testing (obex and retropharyngeal lymph nodes (RLN)). We compared these concentrations between tissues and in relation to CWD status. We established reference intervals (RIs) for these metals and explored their ability to discriminate between CWD-positive and CWD-negative animals. Our results indicate that independent of CWD status, white-tailed deer accumulate higher concentrations of Fe, Mn and Mg in RLN than in obex. White-tailed deer infected with CWD accumulated significantly lower concentrations of Mn and Fe than CWD-negative deer. These patterns differed from other species infected with prion diseases. Overlapping values between CWD positive and negative groups indicate that evaluation of these metals in obex and RLN may not be appropriate as a diagnostic tool for CWD infection in white-tailed deer. Because the CWD-negative deer were included in constructing the RIs, high specificities were expected and should be interpreted with caution. Due to the low sensitivity derived from the RIs, we do not recommend using metal concentrations for disease discrimination.
Keywords: AAS, atomic absorption spectroscopy; AD, Alzheimer disease; ASVCP, American Society for Veterinary Clinical Pathology; BBB, blood brain barrier; CI, confidence intervals; CNS, central nervous system; CP, choroid plexus; CWD, chronic wasting disease; Cu, copper; Fe, iron; ICP-MS, inductively coupled plasma mass spectrometry; IDNR, Illinois Department of Natural Resources; ISTC, Illinois Sustainable Technology Center; ISWS, Illinois State Water Survey; Mg, magnesium; Mn, manganese; PD, Parkinson disease; PRNP, prion protein gene; PrPC, cellular prion protein; PrPSc, abnormal isoform of prion protein; RIs, reference intervals; RLN, retropharyngeal lymph nodes; SOD, superoxide dismutase; SSURGO, Soil Survey Geographic database; STATSGO, State Soil Geographic Database; TSE, transmissible spongiform enchephalopathies; Tf, transferrin; TfR, transferrin receptors; chronic wasting disease; copper; iron; magnesium; manganese; metals imbalance; prion; transmissible spongiform encephalopathy.