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Recent advances in Trace Element Research in Health and Disease D ubrovnik , 18 - 22 Oc t 2015

Macro and microelements as biomarkers of mild cognitive impairment . Recent advances in Trace Element Research in Health and Disease D ubrovnik , 18 - 22 Oc t 2015. Mirjana Babić Leko, mag.biol.mol Department of Neuroscience Croatian Institute for Brain Research

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Recent advances in Trace Element Research in Health and Disease D ubrovnik , 18 - 22 Oc t 2015

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  1. Macro and microelements as biomarkers of mild cognitive impairment  Recent advances in Trace Element Research in Health and DiseaseDubrovnik, 18-22Oct 2015 Mirjana Babić Leko, mag.biol.mol Department of Neuroscience Croatian Institute for Brain Research University of Zagreb Medical School, Zagreb, Croatia

  2. Introduction • Alzheimer's disease (AD) - the major primary cause of dementia • Mild cognitive impairment (MCI) is a syndrome characterized by cognitive impairment without dementia • About 10% MCI patientsconvert to AD annually FDG-PET

  3. High levels of Cu and Zn were detected inside the senile plaques • Fe accumulated intraneuronally Andreasson et al., 2007. Campbell-Switzer-Martin's method

  4. Inorganic copper maybetoxic, not organic copper(Brewer, Front. Aging Neurosci., 2014) • environmental source of inorganic copper: - leaching of copper from copper plumbing - pills containing copper • Zn deficiency is the risk factor for Alzheimer's disease

  5. “Aluminum hypothesis”proposed in the 1960s

  6. Exposure to inorganic mercury, bismuth and silvercan lead to AD-like pathology in noradrenergic locus coeruleus  neurons spreads to neighbouring serotonergic dorsal raphe neurons (Pamphlett and Kum Jew, JAD, 2015) • Hg affects the metabolism of amyloid βandtau protein locus coeruleusneurons

  7. Chelationtherapy for AD treatment is of great interest (Clioquinol, PBT2, DFO, silicates) • IMPORTANT: blood-brain barrier becomes more permeable during ageing • The result is the leakage of metals from plasma into the brain tissue

  8. Objective • differentiate two groups of MCI patients (with normal and pathological levels of Alzheimer's disease protein biomarkers) using 24 macro and microelements measured in cerebrospinal fluid:

  9. Methods • CSF protein biomarkers (Aβ1-42, t-tau, p-tau181, p-tau199, p-tau231 and VILIP-1) measured using ELISA (Laboratory for Developmental Neuropathology) • CSF macro and microelements measured using inductively coupled plasma mass spectroscopy (ICP-MS) (Institute for Medical Research and Occupational Health)

  10. Results • MCI group with pathological Aβ1-42levels had an increase in cerebrospinal fluid levels of:

  11. MCI group with pathological p-tau181levels had an increase in cerebrospinal fluid levels of:

  12. MCI group with pathological p-tau199levels had an increase in cerebrospinal fluid levels of:

  13. MCI group with pathological p-tau231 levels had an increase in cerebrospinal fluid levels of:

  14. MCI group with pathological VILIP-1 levels had an increase in cerebrospinal fluid levels of:

  15. Conclusions • CSF macro and microelements could potentially improve early AD diagnosis established by protein biomarkers • The most promising CSF macro and microelements as biomarkers – Hg, K, Cr, Fe, S, Cu, As and Se • Results should be validated in bigger group of patientsandcompared to the levels of macro and microelements in plasma

  16. Acknowledgements Croatian Institute for Brain Research Goran Šimić, MD, PhD Institute for Medical Research and Occupational Health Jasna Jurasović, PhD Tatjana Orct, PhD University Hospital Centre Zagreb Fran Borovečki, MD, PhD Funded by: • Croatian Science Foundation project IP-2014-09-9730 “Tau protein hyperphosphorylation, aggregation and trans-synaptic transfer in Alzheimer's disease: cerebrospinal fluid analysis and assessment of potential neuroprotectivecompounds“ • http://alztauprotect.hiim.hr Croatian Science Foundation

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