YKL-40 as a Potential Biomarker and a Possible Target in Therapeutic Strategies of Alzheimer’s Disease

Abstract

Background: Growing body of evidence suggests that the pathogenesis of Alzheimer’s disease (AD), a progressing neurodegenerative condition, is not limited to the neuronal compartment, but also involves various immunological mechanisms. Insoluble Aβ aggregates in the brain can induce the activation of microglia, resulting in the synthesis of proinflammatory mediators, which further can stimulate astrocytic expression of YKL-40. Therefore, the aim of the current review is to present up-to-date data about the role of YKL-40 as a biomarker of AD as well as the possibility of therapeutic strategies targeting neuroinflammation.Objective/Methods: We searched PubMed articles for the terms “YKL-40”, “neurodegeneration”, “neuroinflammation” and “Alzheimer’s disease”, and included papers focusing on this review’s scope.Results:Recent studies indicate that CSF concentrations of YKL-40 were significantly higher in AD patients than in cognitively normal individuals and correlated with dementia biomarkers, such as tau proteins and amyloid beta. Determination of YKL-40 CSF concentration may be also helpful in differentiation between types of dementia and in the distinction of patients in the stable phase of MCI from those who progressed to dementia. Moreover, significantly increased levels of YKL-40 mRNA were found in AD brains in comparison with non-demented controls. Additionally, it was suggested that anti-inflammatory treatment might relief the symptoms of AD and slow its progression.Conclusion: Based on the recent knowledge, YKL-40 might be useful as a possible biomarker in the diagnosis and prognosis of AD. Modulation of risk factors and targeting of immune mechanisms, including systemic inflammation could lead to future preventive or therapeutic strategies for AD.

Frontal cortex chitinase and pentraxin neuroinflammatory alterations during the progression of Alzheimer’s disease

“…These observations, when taken together, suggest that chitinase levels vary between cortical regions, perhaps related to the extent and type of AD pathology. Although several studies revealed an increase in CSF CHI3L1 levels, which correlated with CSF markers for tau and amyloid in AD [75,76], we did not find a correlation between CHI3L1 levels/counts and neuritic and diffuse plaques or NFTs. Similar to that in other reports [77], we observed CHI3L1-positive astrocytes in close apposition to amyloid plaques in MCI and AD.…”

Role of Helicobacter pylori infection in the manifestation of old age‐related diseases

“…This is likely because of the chronic inflammation in both the diseases, cross‐linking each other (Xu, Wang, Liu, Cui, & Zhao, ). Consequently, elevated levels of serum YKL‐40 (also known as chitinase‐3‐like protein 1 [CHI3L1]) are a significant marker for many inflammatory diseases, including neurodegenerative ones, such as Alzheimer's (Muszyński, Groblewska, Kulczyńska‐Przybik, Kułakowska, & Mroczko, ). Xu, Wang, Liu, Cui, Lu, et al () demonstrated that CHI3L1 is upregulated in H. pylori ‐positive individuals, presenting vascular dementia and hyperlipidemia in aged individuals.…”

Integrated Proteomics Reveals Brain-Based Cerebrospinal Fluid Biomarkers in Asymptomatic and Symptomatic Alzheimer’s Disease

“…As demonstrated in the volcano plot of Figure 2A, there were a total of 225 proteins with significantly decreased abundance in AD and 303 proteins with significantly increased AD levels. These differentially expressed proteins included several previously identified CSF AD markers, such as microtubule-associated protein tau (MAPT, p=3.52E-08), neurofilament light (NEFL, p=6.56E-03), growth associated protein 43 (GAP43, p=1.46E-05), fatty acid binding protein 3 (FABP3, p=2.00E-05), chitinase 3 like 1 (CHI3L1, p=4.44E-06), neurogranin (NRGN, p=3.43E-04), and VGF nerve growth factor (VGF, p=4.83E-03) [2,[18][19][20][21][22][23]]. Yet, we also identified strongly altered novel targets, such as GDP dissociation inhibitor 1 (GDI1, p=1.54E-10) and SPARC related modular calcium binding 1 (SMOC1, p=6.93E-09).…”