Increased Levels of Chitotriosidase and YKL-40 in Cerebrospinal Fluid from Patients with Alzheimer's Disease

Background: The cerebrospinal fluid (CSF) biomarkers total tau, abnormally phosphorylated tau and amyloid β 1-42 are strongly associated with Alzheimer's disease (AD). Apart from the pathologic hallmarks that these biomarkers represent, other processes such as inflammation and microglial activation are present in the brains of patients with AD. New biomarkers related to these processes could be valuable for the diagnosis and follow-up of AD patients and for the evaluation of inflammation-related pathologies. Aim: The aim of this study was to evaluate the association of inflammatory CSF biomarkers with AD. Methods: Twenty-five AD patients and 25 controls who had a pathological and normal CSF profile of the core AD biomarkers, respectively, were included in this study. CSF levels of chitotriosidase, YKL-40 (also known as chitinase-3-like protein 1) and monocyte chemoattractant protein-1 (MCP-1) were quantified and the levels compared between the groups. Results: AD patients had increased CSF levels of chitotriosidase and YKL-40 (both approximately twice higher than in controls), while the levels of MCP-1 were similar in the AD and control groups. Conclusion: The results indicate that chitotriosidase and YKL-40 may be helpful for the evaluation of cerebral inflammatory activity in AD patients.

[1]  K. Blennow,et al.  CSF levels of YKL-40 are increased in MS and decrease with immunosuppressive treatment , 2014, Journal of Neuroimmunology.

[2]  K. Blennow,et al.  Cerebrospinal fluid biomarkers in cardiac arrest survivors. , 2014, Resuscitation.

[3]  K. Blennow,et al.  Fluid biomarkers in Alzheimer’s disease – current concepts , 2013, Molecular Neurodegeneration.

[4]  A. Singleton,et al.  TREM2 variants in Alzheimer's disease. , 2013, The New England journal of medicine.

[5]  A. Hofman,et al.  Variant of TREM2 associated with the risk of Alzheimer's disease. , 2013, The New England journal of medicine.

[6]  K. Blennow,et al.  Microglial markers are elevated in the prodromal phase of Alzheimer's disease and vascular dementia. , 2012, Journal of Alzheimer's disease : JAD.

[7]  H A Kestler,et al.  Chitinase enzyme activity in CSF is a powerful biomarker of Alzheimer disease , 2012, Neurology.

[8]  Guy C. Brown,et al.  Neuronal Death Induced by Nanomolar Amyloid β Is Mediated by Primary Phagocytosis of Neurons by Microglia* , 2011, The Journal of Biological Chemistry.

[9]  E. Walker,et al.  Diagnostic and Statistical Manual of Mental Disorders , 2013 .

[10]  P. Caramelli,et al.  Chemokines in CSF of Alzheimer's disease patients. , 2011, Arquivos de neuro-psiquiatria.

[11]  K. Blennow,et al.  Cerebrospinal Fluid Microglial Markers in Alzheimer’s Disease: Elevated Chitotriosidase Activity but Lack of Diagnostic Utility , 2011, NeuroMolecular Medicine.

[12]  J. Morris,et al.  The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer's disease , 2011, Alzheimer's & Dementia.

[13]  Ge Li,et al.  Identification and Validation of Novel Cerebrospinal Fluid Biomarkers for Staging Early Alzheimer's Disease , 2011, PloS one.

[14]  Chengjie Xiong,et al.  YKL-40: A Novel Prognostic Fluid Biomarker for Preclinical Alzheimer's Disease , 2010, Biological Psychiatry.

[15]  Nick C Fox,et al.  Revising the definition of Alzheimer's disease: a new lexicon , 2010, The Lancet Neurology.

[16]  G. Landreth,et al.  The role of microglia in amyloid clearance from the AD brain , 2010, Journal of Neural Transmission.

[17]  A. Starkey,et al.  In vivo CHI3L1 (YKL-40) expression in astrocytes in acute and chronic neurological diseases , 2010, Journal of Neuroinflammation.

[18]  M. Weiner,et al.  Cerebrospinal fluid and plasma biomarkers in Alzheimer disease , 2010, Nature Reviews Neurology.

[19]  W. M. van der Flier,et al.  CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment. , 2009, JAMA.

[20]  N. Bresolin,et al.  Intrathecal chemokine synthesis in mild cognitive impairment and Alzheimer disease. , 2006, Archives of neurology.

[21]  H. Hinterhuber,et al.  Measurement of Thirteen Biological Markers in CSF of Patients with Alzheimer’s Disease and Other Dementias , 2005, Dementia and Geriatric Cognitive Disorders.

[22]  J. Eugenín,et al.  Microglial reactivity to β-amyloid is modulated by astrocytes and proinflammatory factors , 2004, Brain Research.

[23]  K. Blennow,et al.  Quantification of tau phosphorylated at threonine 181 in human cerebrospinal fluid: a sandwich ELISA with a synthetic phosphopeptide for standardization , 2000, Neuroscience Letters.

[24]  K. Blennow,et al.  Standardization of measurement of β-amyloid(1-42) in cerebrospinal fluid and plasma , 2000, Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis.

[25]  W. Liao,et al.  Inflammation in Alzheimer's Disease , 1999, Science.

[26]  J. Powers,et al.  Diagnostic Criteria for the Neuropathologic Assessment of Alzheimer’s Disease , 1997, Neurobiology of Aging.

[27]  K. Blennow,et al.  Tau protein in cerebrospinal fluid: a biochemical marker for axonal degeneration in Alzheimer disease? , 1995, Molecular and chemical neuropathology.

[28]  M. Pericak-Vance,et al.  Delayed onset of Alzheimer's disease with nonsteroidal anti-inflammatory and histamine H2 blocking drugs , 1995, Neurobiology of Aging.

[29]  C. Hollak,et al.  Marked elevation of plasma chitotriosidase activity. A novel hallmark of Gaucher disease. , 1994, The Journal of clinical investigation.

[30]  W. McDonald,et al.  Inverse association of anti‐inflammatory treatments and Alzheimer's disease , 1994, Neurology.

[31]  Brian,et al.  Human cartilage gp-39, a major secretory product of articular chondrocytes and synovial cells, is a mammalian member of a chitinase protein family. , 1993, The Journal of biological chemistry.

[32]  J. Wegiel,et al.  Spatial relationships between astrocytes and classical plaque components , 1991, Neurobiology of Aging.

[33]  H. Chui,et al.  Morphologic association between microglia and senile plaque amyloid in Alzheimer's disease , 1990, Neuroscience Letters.

[34]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease , 1984, Neurology.

[35]  D. Selkoe.  Alzheimer's disease. , 2011, Cold Spring Harbor perspectives in biology.

[36]  Khadija Iqbal,et al.  Ultrastructure of the microglia that phagocytose amyloid and the microglia that produce β-amyloid fibrils , 2004, Acta Neuropathologica.

[37]  J. Wegiel,et al.  Ultrastructural studies of the cells forming amyloid in the cortical vessel wall in Alzheimer's disease , 2004, Acta Neuropathologica.