Inflammasome and Cognitive Symptoms in Human Diseases: Biological Evidence from Experimental Research

Cheon, So Yeong; Kim, Jeongmin; Kim, So Yeon; Kim, Eun Jung; Koo, Bon‐Nyeo

doi:10.3390/ijms21031103

Cited by 20 publications

(7 citation statements)

References 134 publications

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“…Of notice, inflammasome activation has been associated with cognitive symptoms in several human diseases ( 18 ) and with cognitive deficits in autoimmune experimental models ( 19 ). As such, we further investigated inflammasome activation as a possible mechanism behind the low-grade inflammation observed and the cognitive deterioration.…”

Section: Resultsmentioning

confidence: 99%

Cognition Is Associated With Peripheral Immune Molecules in Healthy Older Adults: A Cross-Sectional Study

et al. 2020

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Background Cognition in the elderly is heterogeneous. Senescence of the immune system is increasingly considered as a potential player in cognitive performance. We explored here the interplay between cognitive performance and peripheral immune molecules in healthy older individuals. Methods A cross-sectional study of clinically well characterized senior healthy individuals (120; 51–87 years old) previously clustered as “Good” and “Poor” performers based on established tests that evaluate memory and executive function. A plasma concentration of 30 immune molecules was assessed by multiplex analysis and correlated with parameters of cognitive performance. Results Participants with worse cognitive performance (“Poor”) exhibited increased concentrations of IL-1β, IL-8, IL-13, and tumor necrosis factor (TNF) when compared to individuals with a better cognitive performance (“Good”). The cognitive dimensions memory and executive function, when considered separately, displayed a negative association with several immune molecules (IL-1β, IL-1RA, IL-6, IL-13, IP-10, and TNF with memory and only IL-1β with executive function), even controlling for age, sex, years of formal education, mood, and use of anti-inflammatory drugs. Regression analysis showed that several of these molecules (IL-1β, IL-6, IL-8, and IL-13) contribute to predicting whether an individual belongs to the “Good” or “Poor” cognitive performance group. Conclusion These results strengthen the hypothesis that increased concentrations of peripheral immune molecules, like IL-1β, are associated with worse cognitive performance in senior healthy individuals. It further highlights that some poorly studied immune molecules should be considered in the context of cognitive aging, such as IL-13, here revealed as a new player in such interaction.

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Section: Resultsmentioning

confidence: 99%

Cognition Is Associated With Peripheral Immune Molecules in Healthy Older Adults: A Cross-Sectional Study

et al. 2020

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“…We have recently demonstrated increased levels of these IL-18 system components in SMI, associated with increased gene expression of the inflammasome components NLRP3 and NLRC4 in circulating immune cells [67]. The inflammasome is a key innate immune system function that is associated with many human diseases [80]. A growing number of studies suggest that inflammasome activation can influence cognitive functioning, particularly in autoimmune and neurodegenerative diseases [80][81][82][83].…”

Section: Discussionmentioning

confidence: 99%

“…The inflammasome is a key innate immune system function that is associated with many human diseases [80]. A growing number of studies suggest that inflammasome activation can influence cognitive functioning, particularly in autoimmune and neurodegenerative diseases [80][81][82][83]. In addition, experimental studies have shown promise in mitigating cognitive impairment by inhibiting inflammasome activation, which could be a potential treatment target for several pathologies [84].…”

Section: Discussionmentioning

confidence: 99%

Inflammation and cognition in severe mental illness: patterns of covariation and subgroups

et al. 2022

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A potential relationship between dysregulation of immune/inflammatory pathways and cognitive impairment has been suggested in severe mental illnesses (SMI), such as schizophrenia (SZ) and bipolar (BD) spectrum disorders. However, multivariate relationships between peripheral inflammatory/immune-related markers and cognitive domains are unclear, and many studies do not account for inter-individual variance in both cognitive functioning and inflammatory/immune status. This study aimed to investigate covariance patterns between inflammatory/immune-related markers and cognitive domains and further elucidate heterogeneity in a large SMI and healthy control (HC) cohort (SZ = 343, BD = 289, HC = 770). We applied canonical correlation analysis (CCA) to identify modes of maximum covariation between a comprehensive selection of cognitive domains and inflammatory/immune markers. We found that poor verbal learning and psychomotor processing speed was associated with higher levels of interleukin-18 system cytokines and beta defensin 2, reflecting enhanced activation of innate immunity, a pattern augmented in SMI compared to HC. Applying hierarchical clustering on covariance patterns identified by the CCA revealed a high cognition—low immune dysregulation subgroup with predominantly HC (24% SZ, 45% BD, 74% HC) and a low cognition—high immune dysregulation subgroup predominantly consisting of SMI patients (76% SZ, 55% BD, 26% HC). These subgroups differed in IQ, years of education, age, CRP, BMI (all groups), level of functioning, symptoms and defined daily dose (DDD) of antipsychotics (SMI cohort). Our findings suggest a link between cognitive impairment and innate immune dysregulation in a subset of individuals with severe mental illness.

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“…The TOXO-IL-18 association observed in all studied groups combined with the lack of SMI specificity can be indicative of a universal impact of TOXO infections on inflammasome activation with possible implications for the general population. Inflammasome activation has been linked to cognitive dysfunction in neurodegenerative disorders 31 as well as chronic stress, depression, hypothalamic–pituitary–adrenal (HPA) axis dysfunction and systemic illnesses including cardiovascular diseases, diabetes mellitus and autoimmune diseases 32 , 33 . Interestingly, HPA dysfunction has been linked to risk for suicide irrespective of the presence of psychiatric symptoms 34 .…”

Section: Discussionmentioning

confidence: 99%

Toxoplasma gondii infection associated with inflammasome activation and neuronal injury

Andreou,

Steen,

Mørch-Johnsen

et al. 2024

Sci Rep

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Toxoplasma gondii (TOXO) infection typically results in chronic latency due to its ability to form cysts in the brain and other organs. Latent toxoplasmosis could promote innate immune responses and impact brain function. A large body of evidence has linked TOXO infection to severe mental illness (SMI). We hypothesized that TOXO immunoglobulin G (IgG) seropositivity, reflecting previous infection and current latency, is associated with increased circulating neuron-specific enolase (NSE), a marker of brain damage, and interleukin-18 (IL-18), an innate immune marker, mainly in SMI. We included 735 patients with SMI (schizophrenia or bipolar spectrum) (mean age 32 years, 47% women), and 518 healthy controls (HC) (mean age 33 years, 43% women). TOXO IgG, expressed as seropositivity/seronegativity, NSE and IL-18 were measured with immunoassays. We searched for main and interaction effects of TOXO, patient/control status and sex on NSE and IL-18. In the whole sample as well as among patients and HC separately, IL-18 and NSE concentrations were positively correlated (p < 0.001). TOXO seropositive participants had significantly higher NSE (3713 vs. 2200 pg/ml, p < 0.001) and IL-18 levels (1068 vs. 674 pg/ml, p < 0.001) than seronegative participants, and evaluation within patients and HC separately showed similar results. Post-hoc analysis on cytomegalovirus and herpes simplex virus 1 IgG status showed no associations with NSE or IL-18 which may suggest TOXO specificity. These results may indicate ongoing inflammasome activation and neuronal injury in people with TOXO infections unrelated to diagnosis.

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Inflammasome and Cognitive Symptoms in Human Diseases: Biological Evidence from Experimental Research

Cited by 20 publications

References 134 publications

Cognition Is Associated With Peripheral Immune Molecules in Healthy Older Adults: A Cross-Sectional Study

Cognition Is Associated With Peripheral Immune Molecules in Healthy Older Adults: A Cross-Sectional Study

Inflammation and cognition in severe mental illness: patterns of covariation and subgroups

Toxoplasma gondii infection associated with inflammasome activation and neuronal injury

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