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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Acknowledgments
We thank Åsa Källén, Monica Christiansson, Sara Hullberg, Dzemila Secic, Eva Johansson, Mona Palmér and Rita Persson for excellent technical assistance. This study was funded by grants from the Swedish Research Council, the Sahlgrenska University Hospital, the Sahlgrenska Academy, the Lundbeck Foundation, Stiftelsen för Gamla tjänarinnor, Pfannenstills stiftelse, Thuréus stiftelse, the Swedish Association of Persons with Neurological Disabilities, Alzheimer’s Association and the Royal Swedish Academy of Sciences., the Dementia Foundation (Sweden), Uppsala Universitet (Medicinska fakultetens stiftelse för psykiatrisk och neurologisk forskning) and the Swedish Brain Foundation.
Conflict of interests
KB has served in a scientific advisory board for Innogenetics. HZ has served in a scientific advisory board for GlaxoSmithKline. NM has served in a scientific advisory board for Actelion Inc. The other authors have no conflicts of interest.
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Niklas Mattsson, Shahrzad Tabatabaei, and Per Johansson are contributed equally.
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Mattsson, N., Tabatabaei, S., Johansson, P. et al. Cerebrospinal Fluid Microglial Markers in Alzheimer’s Disease: Elevated Chitotriosidase Activity but Lack of Diagnostic Utility. Neuromol Med 13, 151–159 (2011). https://doi.org/10.1007/s12017-011-8147-9
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DOI: https://doi.org/10.1007/s12017-011-8147-9