Abstract
Immunoglobulin G (IgG) functionality can drastically change from anti- to proinflammatory by alterations in the IgG N-glycan patterns. Our previous studies have demonstrated that IgG N-glycans associated with the risk factors of dementia, such as aging, dyslipidemia, type 2 diabetes mellitus, hypertension, and ischemic stroke. Therefore, the aim is to investigate whether the effects of IgG N-glycan profiles on dementia exists in a Chinese Han population. A case–control study, including 81 patients with dementia, 81 age- and gender-matched controls with normal cognitive functioning (NC) and 108 non-matched controls with mild cognitive impairment (MCI) was performed. Plasma IgG N-glycans were separated by ultra-performance liquid chromatography. Fourteen glycan peaks reflecting decreased of sialylation and core fucosylation, and increased bisecting N-acetylglucosamine (GlcNAc) N-glycan structures were of statistically significant differences between dementia and NC groups after controlling for confounders (p < 0.05; q < 0.05). Similarly, the differences for these 14 initial glycans were statistically significant between AD and NC groups after adjusting for the effects of confounders (p < 0.05; q < 0.05). The area under the receiver operating curve (AUC) value of the model consisting of GP8, GP9, and GP14 was determined to distinguish dementia from NC group as 0.876 [95% confidence interval (CI): 0.815–0.923] and distinguish AD from NC group as 0.887 (95% CI: 0.819–0.936). Patients with dementia were of an elevated proinflammatory activity via the significant changes of IgG glycome. Therefore, IgG N-glycans might contribute to be potential novel biomarkers for the neurodegenerative process risk assessment of dementia.
Highlights
Dementia is a major global challenge for health and social care in the 21st century
The levels of systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) of mild cognitive impairment (MCI) group were significantly higher than normal cognitive functioning (NC) group (p < 0.017)
We systematically investigated Immunoglobulin G (IgG) N-glycan profiles in a case–control study including 81 dementia, 108 MCI, and 81 NC participants
Summary
Dementia is a major global challenge for health and social care in the 21st century. It occurs mainly in subjects older than 65 years, making them gradually lose their abilities and become more dependent[1]. Changes in IgG glycosylation participate in many kinds of inflammatory diseases[22,23,24,25], and the molecular mechanism may give rise to the promotion of inflammation[21,26,27]. Considering the fact that the inflammatory role of IgG Nglycosylation and its association with the risk factors of dementia [such as aging, central obesity, dyslipidemia, type 2 diabetes mellitus (T2DM), hypertension, and ischemic stroke]28–34, we hypothesized that these associations might provide a possible explanation for the pathogenesis of dementia in a Chinese Han population. We investigate the associations between IgG N-glycan profiles and inflammation factors including anti-inflammatory (IL-4 and IL-10) and proinflammatory factors [IL-1β, IL-6, CRP, TNF-α, and interferon-gamma (IFN-γ)], which may further explain the role of IgG glycosylation in dementia.
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