Cerebrospinal fluid microglial markers in Alzheimer's disease: elevated chitotriosidase activity but lack of diagnostic utility

阿尔茨海默病的脑脊液小胶质细胞标志物:壳三糖苷酶活性升高但缺乏诊断效用

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作者:Niklas Mattsson, Shahrzad Tabatabaei, Per Johansson, Oskar Hansson, Ulf Andreasson, Jan-Eric Månsson, Jan-Ove Johansson, Bob Olsson, Anders Wallin, Johan Svensson, Kaj Blennow, Henrik Zetterberg

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.

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