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Cytokine and chemokine levels in the cerebrospinal fluid and plasma samples of mild cognitive impairment and Alzheimer's disease subjects

In addition to amyloid β and tau protein pathology, Alzheimer's disease (AD) is characterized by dysregulation of the inflammatory response. The main objective of this study was to find out how the concentrations of immune mediators (cytokines and chemokines) differ between AD, patients with mild cognitive impairment (MCI), and healthy controls (HC) in two different types of samples, cerebrospinal fluid (CSF) and plasma. We also wanted to determine the cytokine profile for each group. Using the Bio-Plex Pro Human Cytokine 48-Plex Screening Panel, we determined the levels of 35 cytokines in CSF and 47 in plasma samples. Twenty-nine AD, 35 MCI, and 40 HC CSF and 102 AD, 37 MCI, and 10 HC plasma samples were analyzed. In the plasma samples, only 4 cytokines differed significantly between the groups (CTACK, IL-12 (p40), IL-4, IL1Rα), whereas analysis of the CSF samples revealed significantly different levels of 15 immune mediators (IL-1β, IL-1α, IL-3, IL-4, IL-7, IL-16, IL-17A, IL-18, IFN-γ, GRO-α, MIP-1β, CTACK, TNF-α, IL-2Rα, IP-10). Most of the mediators whose levels differed significantly were increased in the AD group ; only IP-10 had the highest levels in the MCI group. CSF analysis showed that the AD group was characterized by a pro-inflammatory profile and a higher rate of an adaptive immune response. Higher levels of predominantly pro-inflammatory cytokines (IL-1β, IL-18, MIG, EOTAXIN, MIP-1α, MIP-1β, TNF-β) were associated with higher levels of cognitive deficits. This study has shown that measurement of immune mediators in CSF, but not in plasma, may be a good strategy to track the immune response during disease progression and could be a promising tool for evaluating potential future immune and anti-inflammatory interventions.

Alzheimer’s disease ; inflammation ; immune mediators ; cerebrospinal fluid, multiplex ELISA

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