28 September 2024

 

To better understand the pathophysiology of amnestic Mild Cognitive Impairment (aMCI), a recent study investigated the cytokine network in Thai patients, specifically excluding those with major depression (MDD). The findings challenge the previous belief that inflammation is a key factor in aMCI.

The study, which included 61 aMCI participants and 60 healthy old adults, both without MDD, found that aMCI is characterized by significant immunosuppression, rather than immune activation or inflammation. This manifested as reductions in T helper 1 (Th1) and T cell growth profiles, alongside decreased levels of neuroprotective cytokines such as IL-1$eta$, IL-6, IL-7, IL-12p70, IL-13, GM-CSF, and MCP-1. These cytokines are known to exert neuroprotective effects at physiological concentrations.

 

Interestingly, the study also identified that three neurotoxic chemokines—CCL11, CCL5, and CXCL8—emerged as significant predictors of aMCI. Logistic regression analysis revealed that aMCI was best predicted by combining IL-7, IL-1$eta$, MCP-1, and years of education (all inversely associated), and CCL5 (positively associated). The imbalance between lowered levels of neuroprotective cytokines and chemokines, and relative increases in neurotoxic chemokines, appears to be a key factor in aMCI.

 

These findings are important because they suggest that aMCI may not be driven by inflammation, as previously thought, but rather by immunosuppression and a decrease in neuroprotection. The researchers emphasize that future aMCI research should always control for the confounding effects of affective symptoms, such as MDD, to ensure more accurate results. If these findings are replicated in other populations, the immunosuppression of neuroprotective cytokines/chemokines could become a new drug target to treat aMCI.

 

 This publication received an award for graduate students who completed their studies on time and had international publications, 1st time, Academic Year 2567

This research is supported by the Ratchadapisek Sompoch Fund, Faculty of Medicine, Chulalongkorn University (Grant no. GA66/037); and the 90th Anniversary of Chulalongkorn University Scholarship under the Ratchadapisek Somphot Endowment Fund (Grant no. GCUGR1125661006D), Thailand. MM received funding from the Thailand Science Research and Innovation Fund, Chulalongkorn University (HEA663000016), and a Sompoch Endowment Fund (Faculty of Medicine), MDCU (RA66/016).

Cytokine dysregulation in amnestic mild cognitive impairment

Scientific Reports

10.1038/s41598-024-73099-z

Dr. Michael Maes (dr.michaelmaes@hotmail.com)
Dr. Chavit Tunvirachaisakul (chavit.t@chula.ac.th)

Doctor of Philosophy Program : Clinical Sciences (International Program)

Lecturer Dr. Chavit Tunvirachaisakul, M.D., Ph.D.