title: The role of human kallikrein 6, clusterin and adiponectin as potential blood biomarkers of dementia.
abstract: OBJECTIVE
  Progressive degenerative syndromes which affect brain, altering memory, behavior, cognition and emotion, are commonly defined as dementia. It was suggested that serum human kallikrein 6 (KLK6), clusterin (CLU) and adiponectin (ADPN) in combination with inflammation markers, neuroimaging and neuropsychological testing could assist in discriminating dementia patients from control individuals. Our aim was therefore to compare serum concentrations of KLK6, CLU and ADPN and inflammatory marker, interleukin-6 (IL-6), in patients suffering from Alzheimer's disease (AD), patients with vascular dementia (VAD), cognitively healthy participants (CHP) and those with mild cognitive impairment (MCI).
  
  
  METHODS
  Serum samples were collected from AD, VAD and MCI patients admitted to the University Department of Neurology (Zagreb, Croatia) for regular follow-up. All patients underwent standard neuroimaging procedures including brain CT, neurosonological assessment with intima-media thickness (IMT) and breath holding index (BHI) calculations. Cognitive abilities were tested using standard Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Concentrations of KLK6, CLU, ADPN and IL-6 were determined in all serum samples.
  
  
  RESULTS
  We have recruited a total of 235 participants, divided in 4 groups: AD (N=70), VAD (N=67), MCI (N=48) and CHP (N=50). Serum concentrations of KLK6 (P=0.137), CLU (P=0.178) and ADPN (P=0.268) did not differ between AD, VAD, MCI and cognitively healthy control group of participants, whereas IL-6 was significantly higher in VAD patients than in AD, MCI and CHP individuals (P=0.014). There was no association between investigated biomarkers and clinical patient parameters.
  
  
  CONCLUSIONS
  Serum concentrations of KLK6, CLU and ADPN do not differ between AD, VAD and controls with and without mild cognitive impairment. Higher IL-6 levels in VAD group point to the inflammatory component in the development of vascular dementia. Investigated biomarkers are not associated with neuroimaging findings and neuropsychological patient data.
authors.affiliation: University Department of Chemistry, Medical School University Hospital Sestre milosrdnice, Zagreb, Croatia. Electronic address: lora.dukic@gmail.com.
authors.forename: Lora
authors.initials: L
authors.lastname: Dukic
authors.affiliation: University Department of Chemistry, Medical School University Hospital Sestre milosrdnice, Zagreb, Croatia.
authors.forename: Ana-Maria
authors.initials: AM
authors.lastname: Simundic
authors.affiliation: University Department of Neurology, Medical School University Hospital Sestre milosrdnice, Zagreb, Croatia.
authors.forename: Irena
authors.initials: I
authors.lastname: Martinic-Popovic
authors.affiliation: Medical Biochemistry Laboratory, Policlinic Bonifarm, Zagreb, Croatia.
authors.forename: Sanja
authors.initials: S
authors.lastname: Kackov
authors.affiliation: Department of Clinical Biochemistry, University Health Network, Toronto, Canada.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Diamandis
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada; Department of Laboratory Medicine and Pathobiology, Mount Sinai Hospital, Toronto, Canada.
authors.forename: Ilijana
authors.initials: I
authors.lastname: Begcevic
authors.affiliation: Department of Clinical Biochemistry, University Health Network, Toronto, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada; Department of Laboratory Medicine and Pathobiology, Mount Sinai Hospital, Toronto, Canada.
authors.forename: Eleftherios P
authors.initials: EP
authors.lastname: Diamandis
mesh_terms: D052242:Adiponectin / Q000097:blood*; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood; D015415:Biomarkers / Q000097:blood; D051152:Clusterin / Q000097:blood*; D060825:Cognitive Dysfunction / Q000097:blood; D003704:Dementia / Q000097:blood*; D015140:Dementia, Vascular / Q000097:blood; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D007610:Kallikreins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D015415:Biomarkers; C495242:CLU protein, human; D051152:Clusterin; D015850:Interleukin-6; C103551:KLK6 protein, human; D007610:Kallikreins
keywords: Adiponectin; Clusterin; Dementia; Kallikrein 6