Abstract
BackgroundIncreased plasma YKL-40 has been reported in Alzheimer’s disease (AD), but its levels in other neurodegenerative diseases are unknown. Here, we aimed to investigate plasma YKL-40 in the spectrum of neurodegenerative dementias.MethodsYKL-40 was quantified in the plasma of 315 cases, including healthy controls (HC), neurological disease controls (ND), AD, vascular dementia (VaD), frontotemporal dementia (FTD), sporadic Creutzfeldt-Jakob disease (CJD) and Lewy body dementia (LBD). Diagnostic accuracy in the differential diagnostic context and influence of age and gender was assessed.ResultsHighest YKL-40 levels were detected in CJD, followed by LBD, VaD, AD, FTD, ND and HC. YKL-40 was associated to age but not to sex. After controlling for age, YKL-40 was significantly elevated in CJD compared to HC (p < 0.001), ND, AD and VaD (p < 0.01) and in LBD compared to HC (p < 0.05). In CJD, YKL-40 concentrations were significantly higher at late disease stages.ConclusionsPlasma YKL-40 is significantly elevated in CJD regardless of clinical and genetic parameters, with moderate diagnostic accuracy in the discrimination from control cases. Our study discards a potential use of this biomarker in the differential diagnostic context but opens the possibility to be explored as a marker for CJD monitoring.
Highlights
YKL-40, known as chitinase-3-like protein 1 (CHI3L1), is a secreted glycoprotein expressed in several tissues and involved in activation of the innate immune system and in cell processes in relation to extracellular matrix remodeling [1,2,3]
The study population consisted of 315 plasma agematched cases with the exception of vascular dementia (VaD) cases that were significantly older than healthy controls (HC) (p < 0.01) (Table 1)
Mean YKL-40 concentrations were higher in neurodegenerative dementias compared to HC (84 ng/mL) and neurological disease controls (ND) (95 ng/mL), with highest concentrations detected in Creutzfeldt-Jakob disease (CJD) (189 ng/mL), followed by Lewy body dementia (LBD) (167 ng/mL), VaD (140 ng/ mL), Alzheimer’s disease (AD) (133 ng/mL) and frontotemporal dementia (FTD) (125 ng/mL) (Table 1)
Summary
YKL-40, known as chitinase-3-like protein 1 (CHI3L1), is a secreted glycoprotein expressed in several tissues and involved in activation of the innate immune system and in cell processes in relation to extracellular matrix remodeling [1,2,3]. Cerebrospinal fluid (CSF) concentrations of YKL-40 are significantly increased in sporadic Creutzfeldt-Jakob disease (CJD) and Alzheimer’s disease (AD), while other neurodegenerative dementias such as frontotemporal dementia (FTD), Lewy body dementia (LBD) and vascular dementia (VaD) show normal to slightly altered levels [4,5,6]. In AD, plasma YKL-40 concentrations were reported to be increased, but with limited utility as a diagnostic marker [7] presenting moderate effect sizes according to meta-analysis studies [8]. The levels of plasma YKL-40 in other neurodegenerative dementias are unknown. We evaluated the accuracy of plasma YKL-40 in the discrimination of neurodegenerative dementias from different etiologies. Increased plasma YKL-40 has been reported in Alzheimer’s disease (AD), but its levels in other neurodegenerative diseases are unknown. We aimed to investigate plasma YKL-40 in the spectrum of neurodegenerative dementias
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