Reduced cerebrospinal fluid concentration of interleukin-12/23 subunit p40 in patients with cognitive impairment

Abstract

BackgroundThe role of inflammation in Alzheimer’s disease (AD) and other cognitive disorders is unclear. In a well-defined mono-center population, we measured cytokines and chemokines in paired serum and cerebrospinal fluid (CSF) samples.MethodsConsecutive patients with AD (n = 30), stable mild cognitive impairment (SMCI, n = 11), other dementias (n = 11), and healthy controls (n = 18) were included. None of the subjects was treated with glucocorticoids, cholinesterase inhibitors, or non-steroidal anti-inflammatory drugs. Serum and CSF concentrations of interleukin-6 (IL-6), IL-8, IL-12/23 p40, IL-15, IL-16, vascular endothelial growth factor-A (VEGF-A), and three chemokines were measured using a multiplex panel.ResultsAfter correction for multiple comparisons, only CSF IL-12/23 p40 concentration differed significantly between the total patient group (n = 52) and controls (n = 18; p = 0.002). Further analyses showed that CSF IL-12/23 p40 concentration was decreased in all patient subgroups (AD, other dementias, and SMCI) compared to healthy controls (p < 0.01, p < 0.05, and p < 0.05, respectively). In the total study population (n = 70), CSF IL-12/23 p40 concentrations correlated positively with CSF concentrations of β-amyloid1-42 (Aβ1–42) and phosphorylated tau protein (P-tau) whereas in AD patients (n = 30), CSF IL-12/23 p40 only correlated positively with CSF P-Tau (r = 0.46, p = 0.01).ConclusionsMost cytokines and chemokines were similar in patients and controls, but CSF IL-12/23 subunit p40 concentration was decreased in patients with cognitive impairment, and correlated with markers of AD disease status. Further studies are needed to evaluate the role of CSF IL-12/23 p40 in other dementias and SMCI.

Chronic HIV-1 Tat exposure alters anterior cingulate cortico-basal ganglia-thalamocortical synaptic circuitry, associated behavioral control, and immune regulation in male mice

“…Furthermore, Tat-induced expression of CCL4 and IL-17A interacted with exposure time to predict increased FST mobility after 2 weeks of exposure, while predicting a decrease after 8 weeks of Tat. The correlation of IL-12p40 and IL-17A expression in the PFC with Tat-induced dysfunctional coping aligns with previous reports indicating their importance in potentially mediating depression and cognitive impairment and suggest they might be therapeutic targets for HAND ( Johansson et al, 2017 ; McGeachy et al, 2019 ). Prolonged Tat induction in the present study increased CCL5, CCL11, 1L-1β, and IL-6 levels in the striatum.…”

A blood-based biomarker panel indicates IL-10 and IL-12/23p40 are jointly associated as predictors of β-amyloid load in an AD cohort

“…It is not known if this is consistent in the brain, but it was demonstrated in other mouse models that inhibition of IL-12/23 p40 was associated with reduced Aβ levels 57 , 58 . This seems to agree with a recent small scale study using CSF from human participants that showed a positive correlation of IL-12/23 p40 with CSF Aβ1-42 59 , and our own current work here. This evidence strengthens the connection between brain amyloid load and the immune system.…”

Microarray Expression Profiles of lncRNAs and mRNAs in Postoperative Cognitive Dysfunction

“…In concur with other recent works which presented evidences of histone deacetylase-2 as player in stress-induced cognitive impairment via histone deacetylation and PI3K/AKT pathway modulation ( Verma et al, 2017 ; Wu et al, 2017 ), our results are consent with these published studies. However, the recognized biological processes leading to the pathogenesis of POCD, such as inflammation, stress, and apoptosis ( Tian et al, 2015 ; Johansson et al, 2017 ; Zhang et al, 2018 ), are less prominent in our results. Sirtuin1 (SIRT1) is a deacetylase protein that reported to mediate hippocampal neuronal apoptosis in mice and causing cognitive deficit ( Min et al, 2018 ).…”

“… Yi et al (2015) reported the close relatedness of inflammatory response with the changes in cognitive function in cardiopulmonary bypass patients ( Yi et al, 2015 ). In a similar manner, interleukin-12 and its receptor were demonstrated to influence cognitive function ( Johansson et al, 2017 ; Vonder Haar et al, 2017 ; Wu et al, 2017 ). Likewise, cytokines and cytokines receptor participate apoptosis and immune regulation through Jak-STAT signaling pathway by specifically activate STAT4 ( Darnell et al, 1994 ; Kang and Kang, 2008 ).…”