Body fluid cytokine levels in mild cognitive impairment and Alzheimer's disease: a comparative overview

Abstract

This article gives a comprehensive overview of cytokine and other inflammation associated protein levels in plasma, serum and cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). We reviewed 118 research articles published between 1989 and 2013 to compare the reported levels of 66 cytokines and other proteins related to regulation and signaling in inflammation in the blood or CSF obtained from MCI and AD patients. Several cytokines are evidently regulated in (neuro-) inflammatory processes associated with neurodegenerative disorders. Others do not display changes in the blood or CSF during disease progression. However, many reports on cytokine levels in MCI or AD are controversial or inconclusive, particularly those which provide data on frequently investigated cytokines like tumor necrosis factor alpha (TNF-α) or interleukin-6 (IL-6). The levels of several cytokines are possible indicators of neuroinflammation in AD. Some of them might increase steadily during disease progression or temporarily at the time of MCI to AD conversion. Furthermore, elevated body fluid cytokine levels may correlate with an increased risk of conversion from MCI to AD. Yet, research results are conflicting. To overcome interindividual variances and to obtain a more definite description of cytokine regulation and function in neurodegeneration, a high degree of methodical standardization and patients collective characterization, together with longitudinal sampling over years is essential.

Fig. 1

Hypothetical time course of CSF cytokine expression in AD. Graphs display the estimated CSF concentration changes of amyloid and tau protein during the development of AD, as described by others [142]. As different cytokines and other inflammatory proteins appear to display different changes in CSF levels during disease development, they might be divided into groups: First, cytokines like IL-1α or IL-2 which might remain unchanged in AD; Second, cytokines like IL-1β, IL-6 or TNF-α which might increase slowly during disease progression; third, cytokines like IL-18, MCP-1 or IP-10 which might show a peak at certain disease stages, especially at time of MCI to AD conversion. However, data becomes scarce for early disease stages. To test this hypothesis and the grouping of cytokines, longitudinal CSF sampling from individuals at risk of dementia over years would be the most efficient way