Abstract
IntroductionInflammatory processes have previously been shown to influence cognition and progression of dementia. An involvement of interleukin (IL)-6 has in particular been suggested as altered levels of IL-6 in cerebrospinal fluid (CSF) have been found in patients with Alzheimer’s disease (AD). Also, an association between cognitive decline and levels of IL-6 in CSF have been reported. The aim of the present study was to investigate whether patients clinically diagnosed with dementia with Lewy bodies (DLB) display altered CSF IL-6 levels in comparison with patients with AD and control subjects without dementia and whether the IL-6 levels are correlated with cognitive status and biomarkers for AD and synucleinopathy.MethodsTo analyse CSF of patients with AD (n = 45), patients with DLB (n = 29) and control subjects without dementia (n = 36), we used immunoassays to measure levels of IL-6 (multiplex electrochemiluminescence); AD markers phosphorylated tau, total tau and amyloid-β1–42 (enzyme-linked immunosorbent assay [ELISA]); and α-synuclein (ELISA). Cognitive status was evaluated using the Mini Mental State Examination (MMSE).ResultsOur analysis showed significantly lower levels of IL-6 in CSF from patients with DLB than in CSF from patients with AD and control subjects without dementia. The IL-6 levels were also negatively correlated with MMSE and positively correlated with α-synuclein CSF levels.ConclusionsOur findings support previous studies by demonstrating a link between inflammatory processes and dementia progression and further strengthen the hypothesis that IL-6 is involved in dementia pathology and cognitive decline.
Highlights
Inflammatory processes have previously been shown to influence cognition and progression of dementia
Our findings support previous studies by demonstrating a link between inflammatory processes and dementia progression and further strengthen the hypothesis that IL-6 is involved in dementia pathology and cognitive decline
We examined the relationship between cerebrospinal fluid (CSF) IL-6 levels and Mini Mental State Examination (MMSE) scores to investigate whether IL-6 may be an underlying factor involved in the cognitive changes seen in patients with dementia with Lewy bodies (DLB)
Summary
Inflammatory processes have previously been shown to influence cognition and progression of dementia. An involvement of interleukin (IL)-6 has in particular been suggested as altered levels of IL-6 in cerebrospinal fluid (CSF) have been found in patients with Alzheimer’s disease (AD). The increase in IL-6 secretion has been shown to be beneficial [1,2,3,4,5], but sometimes detrimental [6,7,8,9], for the neuronal network, depending on variables such as cytokine concentration, brain region, target cell and developmental stage. Results of clinical studies point towards a relationship between IL-6 and brain function, as cognitive decline has been associated with elevated levels of IL-6 in plasma and/or serum [13,14,15,16] and cerebrospinal fluid (CSF) [17, 18]. Examinations of post-mortem brain tissue from patients with Alzheimer’s disease (AD) have revealed activated glial cells as well as elevated expression of IL-6 adjacent to amyloid-β (Aβ) forming senile plaques [19, 20], a hallmark of AD pathology [21]
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