Increased YKL-40 but Not C-Reactive Protein Levels in Patients with Alzheimer’s Disease

Abstract

Neuroinflammation is a common feature in Alzheimer’s (AD) and Parkinson’s (PD) disease. In the last few decades, a testable hypothesis was proposed that protein-unfolding events might occur due to neuroinflammatory cascades involving alterations in the crosstalk between glial cells and neurons. Here, we tried to clarify the pattern of two of the most promising biomarkers of neuroinflammation in cerebrospinal fluid (CSF) in AD and PD. This study included cognitively unimpaired elderly patients, patients with mild cognitive impairment, patients with AD dementia, and patients with PD. CSF samples were analyzed for YKL-40 and C-reactive protein (CRP). We found that CSF YKL-40 levels were significantly increased only in dementia stages of AD. Additionally, increased YKL-40 levels were found in the cerebral orbitofrontal cortex from AD patients in agreement with augmented astrogliosis. Our study confirms that these biomarkers of neuroinflammation are differently detected in CSF from AD and PD patients.

White Blood Cell and Platelet Counts Are Not Suitable as Biomarkers in the Differential Diagnostics of Dementia

“…The significance of inflammatory markers such as CRP, which can readily be determined in peripheral blood, has also been investigated repeatedly, especially in AD, with partly contradictory results [ 26 , 35 , 36 ]. While several studies showed significantly higher CRP levels in patients with AD than in healthy controls, a study by Nilsson et al showed that patients with VD had significantly higher CRP levels than those with AD [ 37 , 38 ].…”

Neuroprotective Epigenetic Changes Induced by Maternal Treatment with an Inhibitor of Soluble Epoxide Hydrolase Prevents Early Alzheimer′s Disease Neurodegeneration

“…In contrast to other sirtuins, sirtuin 2 promotes neurodegeneration in experimental models [ 61 ] and some SIRT2 variants increase AD risk [ 62 ]. Chitinase-like 1 is a marker of reactive gliosis and the innate immune response which shows human counterpart (chitinase 3-like 1 or YKL-40) increases in the CSF of AD patients, although changes in postmortem AD brain are controversial [ 63 , 64 ]. Young female offspring also showed a general increase in protein levels of GFAP and EGR1 as compared to the male offspring.…”

“…Young female offspring also showed a general increase in protein levels of GFAP and EGR1 as compared to the male offspring. The reactive astrocyte marker GFAP is increased in AD brain and in AD mouse models [ 32 , 63 ]. GFAP and chitinase-like 1 are differentially related to AD but both may mediate brain atrophy and cognitive impairment [ 65 ].…”

Inflammation—Cause or consequence of late onset Alzheimer’s disease or both? A review of the evidence

“…Early findings have revealed that Aβ can activate microglia and astrocytes, causing inflammatory responses such as IL-1β production and increased expression of cyclooxygenase and inducible nitric oxide synthase (iNOS) to kill neurons. 51 Recent in vivo studies of AD patients also indicated that Aβ pathology was closely associated with astrocyte activation biomarkers such as chitinase-3-like protein 1 (YKL-40) 52 and glial fibrillary acidic protein (GFAP), 53 indirectly supporting the association between Aβ and astrocyte activation during AD development. Of note, Aβ needs a pre-stimulated environment to show its maximal pro-inflammatory potential.…”