The Diagnostic Role of Serum Inflammatory and Soluble Proteins on Dementia Subtypes: Correlation with Cognitive and Functional Decline

Abstract

In the past years, the possible involvement of inflammation in the pathogenesis of dementia has been the subject of several investigations. However there are restricted data about the profile of the inflammatory and soluble proteins in well evaluated Alzheimer’s disease (AD), vascular dementia (VD), mild cognitive impairment (MCI) and healthy controls. There are also no reliable data regarding the relationship between the overlapping protein levels and cognitive or functional decline. We measured levels of IL-1β, IL-2, IL-6, IL-18, TNF-α, β-Amlyloid 1–40 and α1-antichymotrypsin levels in plasma in groups of total 82 subjects with AD, MCI, VD and controls using enzyme-linked immunosorbent assay (ELISA) method. Our study samples showed high levels of proinflammatory cytokine levels (especially IL-18) in all patient groups but only high levels of α1-antichymotrypsine in VD patients compared to controls. There is no significant correlation between the laboratory and clinical variables except for a link between IL-1β and NPI scores of AD. In conclusion, this study yielded evidence of some shared mechanisms underlying AD and VD and thus motivates further studies of inflammatory markers in various types of dementia and MCI.

Genetic predisposition to higher production of interleukin-6 through -174 G > C polymorphism predicts global cognitive decline in oldest-old with cognitive impairment no dementia

“…Additionally, Adriansen et al 24 studied global functional decline in a population-based cohort of Belgium oldest-old using an extensive panel of inflammatory markers According to their findings, IL-6 was the only inflammatory marker with an independent association with functional decline, in a dose-dependent manner 24 . Event thought there are conflicting results regarding the role of IL-6 levels and age-associated cognitive and functional performance 25,26 , our findings stand in accordance with a growing set of studies that reinforce the association between this cytokine and age-related outcomes.…”

The role of inflammasome in Alzheimer's disease

“…The mRNA and protein levels of IL-18 increase significantly in astrocytes, microglia and neurons that co-localized with Aβ plaques in the brains of AD patients (Ojala et al, 2009). IL-18 is elevated significantly in the plasma of mild cognitively impaired and AD patients (Malaguarnera et al, 2006; Ozturk et al, 2007). Moreover, a significant increase in IL-18 is observed in stimulated mononuclear cells and macrophages of peripheral blood from AD patients (Bossu et al, 2008; Di Rosa et al, 2006), as well as in the blood of patients with ischemic heart disease, type-2 diabetes, and obesity, which are risk factors for AD (Sutinen et al, 2012).…”

Interleukin 18 activates MAPKs and STAT3 but not NF-κB in hippocampal HT-22 cells

“…These include neuroinflammatory (Abdul-Careem et al, 2006; von Giesen et al, 2004) and autoimmune diseases (Huang et al, 2004; Losy and Niezgoda, 2001) as well as neurodegenerative (Bossu et al, 2008; Iannello et al, 2009; Sugama et al, 2004; Sutinen et al, 2012) and neuropsychiatric disorders (Haastrup et al, 2012; Kroes et al, 2006; Lu et al, 2004; Kokai et al, 2002; Shelton et al, 2011). Indeed, increased levels of IL-18 were found in the presence of cognitive dysfunction (Oztürk et al, 2007; Kumar et al, 2007) and for Alzheimer’s disease the IL-18 levels correlate with cognitive decline (Bossu et al 2008), providing evidence linking IL-18 also to cognitive impairment. Moreover, IL-18 actions shift from promoting neuroinflammation and/or neurodegeneration to promoting neuroprotection; for example, after kainic acid administration or following status epilepticus ( Andoh et al, 2008, Jung et al, 2012, Ryu el al., 2010, Yaguchi et al, 2010, Zhang et al, 2007), demonstrating that IL-18/ IL-18R system act within the brain in a more complex way than simple disease-promoting or inhibiting and that its outcomes depend on the concentration, cell targets, stimulus duration as well as other disease-associated factors.…”