Transcript Annual meeting of the COST ACTION CM1103 Neuropathology and

Recent advances in Trace Element Research in Health and Disease
Dubrovnik, 18-22 Oct 2015
Macro and microelements as
biomarkers of mild cognitive
impairment
Mirjana Babić Leko, mag.biol.mol
Department of Neuroscience
Croatian Institute for Brain Research
University of Zagreb Medical School, Zagreb, Croatia
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 patients convert to AD annually
FDG-PET
• High levels of Cu and Zn were detected inside the senile plaques
• Fe accumulated intraneuronally
Andreasson et al., 2007.
Campbell-Switzer-Martin's method
• Inorganic copper may be toxic, 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
• “Aluminum hypothesis” proposed in the 1960s
• Exposure to inorganic mercury, bismuth and silver can
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 β and tau protein
locus coeruleus neurons
• Chelation therapy 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
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:
Methods
• CSF protein biomarkers (Aβ1-42, ttau, 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)
Results
• MCI group with pathological Aβ1-42 levels had an
increase in cerebrospinal fluid levels of:
• MCI group with pathological p-tau181 levels had an
increase in cerebrospinal fluid levels of:
• MCI group with pathological p-tau199 levels had an
increase in cerebrospinal fluid levels of:
• MCI group with pathological p-tau231 levels had an
increase in cerebrospinal fluid levels of:
• MCI group with pathological VILIP-1 levels had an
increase in cerebrospinal fluid levels of:
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
patients and compared to the levels of macro and
microelements in plasma
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
Croatian Science Foundation
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 neuroprotective
compounds“
• http://alztauprotect.hiim.hr