title: Pro-inflammatory S100A9 Protein as a Robust Biomarker Differentiating Early Stages of Cognitive Impairment in Alzheimer's Disease.
abstract: Pro-inflammatory protein S100A9 was established as a biomarker of dementia progression and compared with others such as Aβ(1-42) and tau-proteins. CSF samples from 104 stringently diagnosed individuals divided into five subgroups were analyzed, including nondemented controls, stable mild cognitive impairment (SMCI), mild cognitive impairment due to Alzheimer's disease (MCI-AD), Alzheimer's disease (AD), and vascular dementia (VaD) patients. ELISA, dot-blotting, and electrochemical impedance spectroscopy were used as research methods. The S100A9 and Aβ(1-42) levels correlated with each other: their CSF content decreased already at the SMCI stage and declined further under MCI-AD, AD, and VaD conditions. Immunohistochemical analysis also revealed involvement of both Aβ(1-42) and S100A9 in the amyloid-neuroinflammatory cascade already during SMCI. Tau proteins were not yet altered in SMCI; however their contents increased during MCI-AD and AD, diagnosing later dementia stages. Thus, four biomarkers together, reflecting different underlying pathological causes, can accurately differentiate dementia progression and also distinguish AD from VaD.
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University , Umeå 901 87, Sweden.
authors.forename: Istvan
authors.initials: I
authors.lastname: Horvath
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University , Umeå 901 87, Sweden.|Department of Physics, Umeå University , Umeå 901 87, Sweden.
authors.forename: Xueen
authors.initials: X
authors.lastname: Jia
authors.affiliation: Department of Neuropsychiatry, Skaraborg Central Hospital , Falköping 521 85, Sweden.|Department of Internal Medicine, Sahlgrenska Academy, University of Gothenburg , Gothenburg 413 45, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Johansson
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University , Umeå 901 87, Sweden.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University , Umeå 901 87, Sweden.|Department of Pathology, Sumy State University , Sumy 40000, Ukraine.
authors.forename: Roman
authors.initials: R
authors.lastname: Moskalenko
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University , Umeå 901 87, Sweden.
authors.forename: Andreas
authors.initials: A
authors.lastname: Steinau
authors.affiliation: Department of Pharmacology and Clinical Neuroscience, Umeå University , Umeå 901 87, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Forsgren
authors.affiliation: Department of Physics, Umeå University , Umeå 901 87, Sweden.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wågberg
authors.affiliation: Department of Internal Medicine, Sahlgrenska Academy, University of Gothenburg , Gothenburg 413 45, Sweden.|Department of Endocrinology, Skaraborg Central Hospital , Skövde 541 85, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Svensson
authors.affiliation: Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg , Mölndal 431 80, Sweden.|University College London , Institute of Neurology, Queen Square, London WC1E 6BT, United Kingdom.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University , Umeå 901 87, Sweden.
authors.forename: Ludmilla A
authors.initials: LA
authors.lastname: Morozova-Roche
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid; D040502:Calgranulin B / Q000134:cerebrospinal fluid*; D003072:Cognition Disorders / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000209:etiology; D018450:Disease Progression; D004637:Emergency Services, Psychiatric; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D013223:Statistics as Topic; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D040502:Calgranulin B; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
keywords: Alzheimer’s disease; Aβ1−42; S100A9; amyloid; biomarkers; cerebrospinal fluid; inflammation; mild cognitive impairment