title: Cerebrospinal fluid microglial markers in Alzheimer's disease: elevated chitotriosidase activity but lack of diagnostic utility.
abstract: Activated microglial cells, which are the resident macrophages of the central nervous system, surround amyloid β-plaques in Alzheimer's disease (AD) brains. Inflammation including microglial activation may contribute in AD pathogenesis, and biomarkers for this process may thus be of value to study AD pathogenesis and might facilitate development of therapies targeting these cells. We therefore examined cerebrospinal fluid (CSF) biomarkers in patients with AD, other dementias, mild cognitive impairment and in healthy controls. Samples were analyzed for markers with known association to macrophage activity, including chitotriosidase, YKL-40 (CHI3L1, HC gp-39) and chemokine CC motif ligand 2 (CCL2, MCP1). Patients with AD had higher chitotriosidase activity than controls and patients with stable mild cognitive impairment, consistent with the presence of activated microglial cells in AD brains, but with large overlaps between groups. CCL2 and YKL-40 concentrations did not differ among groups. Microglial markers are unlikely to be useful for AD diagnosis, but might be useful for identification of distinct subgroups of patients, and for the development and implementation of drugs targeting microglial pathology.
authors.affiliation: Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, S-431 80 Mölndal, Sweden. niklas.mattsson@neuro.gu.se
authors.forename: Niklas
authors.initials: N
authors.lastname: Mattsson
authors.forename: Shahrzad
authors.initials: S
authors.lastname: Tabatabaei
authors.forename: Per
authors.initials: P
authors.lastname: Johansson
authors.forename: Oskar
authors.initials: O
authors.lastname: Hansson
authors.forename: Ulf
authors.initials: U
authors.lastname: Andreasson
authors.forename: Jan-Eric
authors.initials: JE
authors.lastname: Månsson
authors.forename: Jan-Ove
authors.initials: JO
authors.lastname: Johansson
authors.forename: Bob
authors.initials: B
authors.lastname: Olsson
authors.forename: Anders
authors.initials: A
authors.lastname: Wallin
authors.forename: Johan
authors.initials: J
authors.lastname: Svensson
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000201:enzymology / Q000473:pathology*; D015415:Biomarkers / Q000134:cerebrospinal fluid / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D006596:Hexosaminidases / Q000096:biosynthesis* / Q000134:cerebrospinal fluid*; D006801:Humans; D008264:Macrophages / Q000201:enzymology / Q000473:pathology; D008297:Male; D017628:Microglia / Q000201:enzymology* / Q000473:pathology; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D015415:Biomarkers; D006596:Hexosaminidases; C086400:chitotriosidase