Abstract
BackgroundThe innate immune system is known to be involved early in the pathogenesis of Alzheimer’s disease (AD) and other neurodegenerative disorders. The inflammatory response in the central nervous system can be measured postmortem or through a series of inflammatory mediator surrogates. YKL-40 (also named Chitinase-3-like I) has been frequently investigated in body fluids as a surrogate marker of neuroinflammation in AD and other neurological disorders. However, the expression pattern of YKL-40 in the human brain with neurodegenerative pathology remains poorly investigated. Our aim was to study the cellular expression pattern of YKL-40 in the brain of patients with clinical and neuropathological criteria for AD (n = 11); three non-AD tauopathies: Pick’s disease (PiD; n = 8), corticobasal degeneration (CBD; n = 8) and progressive supranuclear palsy (PSP; n = 9) and a group of neurologically healthy controls (n = 6).MethodsSemiquantitative neuropathological evaluation and quantitative confocal triple immunofluorescence studies were performed. An in-house algorithm was used to detect and quantify pathology burden of random regions of interest on a full tissue-section scan. Kruskal-Wallis and Dunn’s multiple comparison tests were performed for colocalization and quantification analyses.ResultsWe found that brain YKL-40 immunoreactivity was observed in a subset of astrocytes in all four diseases and in controls. There was a strong colocalization between YKL-40 and the astroglial marker GFAP but not with neuronal nor microglial markers. Intriguingly, YKL-40-positive astrocytes were tau-negative in PSP, CBD and PiD. The number of YKL-40-positive astrocytes was increased in tauopathies compared with that in controls. A positive correlation was found between YKL-40 and tau immunoreactivities.ConclusionsThis study confirms that YKL-40 is expressed by a subset of astrocytes in AD and other tauopathies. YKL-40 expression is elevated in several neurodegenerative conditions and correlates with tau pathology.
Highlights
The innate immune system is known to be involved early in the pathogenesis of Alzheimer’s disease (AD) and other neurodegenerative disorders
YKL-40 is expressed by astrocytes in human brain tissue We first examined the cellular expression of YKL-40 in human brain tissue from an AD patient and a healthy control
Using a double immunofluorescence technique, we investigated the colocalization between YKL-40 and three different markers: Microtubule-associated protein 2 (MAP2) as a neuronal marker, Glial fibrillary acidic protein (GFAP) as an astroglial marker and IBA-1 as a microglial marker (Fig. 1)
Summary
The innate immune system is known to be involved early in the pathogenesis of Alzheimer’s disease (AD) and other neurodegenerative disorders. YKL-40 ( named Chitinase-3-like I) has been frequently investigated in body fluids as a surrogate marker of neuroinflammation in AD and other neurological disorders. One of the proteins that has been frequently measured in body fluids as a surrogate marker of neuroinflammation in AD and other neurological disorders is YKL-40 ( named Chitinase 3-like I) [7, 8]. Increased levels of YKL40 were found in the preclinical stages of AD [13, 14] indicating that the immune system activation occurs early in the disease. These studies have shown that CSF levels of YKL-40 and tau strongly correlate [11, 12]. Additional studies have indicated that YKL-40 is elevated in the CSF of patients with other tauopathies, such as frontotemporal dementia (FTD), corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) [11, 13, 15, 16]
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