The Inflammatory Marker YKL-40 Is Elevated in Cerebrospinal Fluid from Patients with Alzheimer's but Not Parkinson's Disease or Dementia with Lewy Bodies.
A major difference in the revised diagnostic criteria for Alzheimer's disease (AD) is the incorporation of biomarkers to support a clinical diagnosis and allow the identification of preclinical AD due to AD neuropathological processes. However, AD-specific fluid biomarkers which specifically distinguish clinical AD dementia from other dementia disorders are still missing. Here we aimed to evaluate the disease-specificity of increased YKL-40 levels in cerebrospinal fluid (CSF) from AD patients with mild to moderate dementia (n = 49) versus Parkinson's disease (PD) (n = 61) and dementia with Lewy bodies (DLB) patients (n = 36), and non-demented controls (n = 44). Second we aimed to investigate whether altered YKL-40 levels are associated with CSF levels of other inflammation-associated molecules. When correcting for age, AD patients exhibited 21.3%, 27.7% and 38.8% higher YKL-40 levels compared to non-demented controls (p = 0.0283), DLB (p = 0.0027) and PD patients (p<0.0001). The AD-associated increase in YKL-40 was not associated with CSF P-tau, T-tau or Aβ42. No relationship between increased YKL-40 and levels of the astrocytic marker glial-fibrillary acidic protein (GFAP), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1) and interferon gamma-induced protein 10 (IP-10) could be identified. Our results confirm previous reports of an age-associated increased in CSF YKL-40 levels and further demonstrate increased CSF YKL-40 in AD patients versus non-demented controls and patients with DLB or PD. The increase in YKL-40 levels in the AD patients was unrelated to the established CSF AD biomarkers and the inflammatory markers GFAP, MCP-1, IP-10 and IL-8, proposing YKL-40 as a marker of yet to be identified AD-related pathological processes.
Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
Malin
M
Wennström
Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden; Department of Neurology, Skåne University Hospital, Lund, Sweden.
Yulia
Y
Surova
Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden; Department of Neurology, Skåne University Hospital, Lund, Sweden.
Sara
S
Hall
Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden; Department of Neurology, Skåne University Hospital, Lund, Sweden.
Christer
C
Nilsson
Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden; Memory Clinic, Skåne University Hospital, Malmö, Sweden.
Lennart
L
Minthon
Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden; Memory Clinic, Skåne University Hospital, Malmö, Sweden.
Oskar
O
Hansson
Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden; Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida, United States of America.
Henrietta M
HM
Nielsen
D054392:Adipokines / Q000134:cerebrospinal fluid*; D000367:Age Factors; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000276:immunology*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D018925:Chemokines / Q000134:cerebrospinal fluid; D000071451:Chitinase-3-Like Protein 1; D003704:Dementia / Q000134:cerebrospinal fluid / Q000276:immunology*; D006801:Humans; D037102:Lectins / Q000134:cerebrospinal fluid*; D020961:Lewy Body Disease / Q000134:cerebrospinal fluid / Q000276:immunology*; D009419:Nerve Tissue Proteins / Q000134:cerebrospinal fluid; D010300:Parkinson Disease / Q000134:cerebrospinal fluid / Q000276:immunology*
D054392:Adipokines; D015415:Biomarkers; C084533:CHI3L1 protein, human; D018925:Chemokines; D000071451:Chitinase-3-Like Protein 1; D037102:Lectins; D009419:Nerve Tissue Proteins