Inflammasome and innate immunity biomarkers in patients affected by mild cognitive impairment due to Alzheimer's disease.
- Authors
- Publication Date
- Dec 12, 2023
- Source
- Hal-Diderot
- Keywords
- Language
- English
- License
- Unknown
- External links
Abstract
This work project is a focus study centered on the inflammatory response implication in Alzheimer's disease (AD) development at an early disease onset. The primary objective was to investigate the inflammatory signature in pre-demented subject suffering from mild cognitive impairment (MCI). To do so, soluble inflammatory biomarkers were measured in the serum and cerebrospinal fluid of three different populations using different quantitative immunoassays along with one semi-quantitative profiling method. Then, in-group comparisons and correlations between biomarkers were performed with statistical analyses. Results confirmed that MCI due to AD patients presented a higher inflammatory status compared to a healthy population. Additionally, data suggested that two inflammatory responses are occurring at the beginning of the dementia, one in the systemic circulation and one in the central nervous system. Soluble biomarkers associated with astrogliosis (glial fibrillary acidic protein (GFAP), chitinase 3 like-1 YKL-40), microgliosis (soluble triggering receptor on myeloid cells 2 (sTREM-2)) and neurodegenerative process (neurofilament light chain protein (NFL), total Tau protein (tTau)) were significantly increased in the cerebrospinal fluid of the MCI patients. In addition, systemic inflammatory biomarkers were increased in MCI serum as well compared to healthy controls, especially the IL- (Interleukin) 1β and IL-8. As a secondary objective, focus was drawn on the role of IL-1β and the inflammasome pathway, as MCI patients demonstrated higher peripheral IL-1β concentration. In addition, IL-8 confirmed potential role and infiltration of monocytes and neutrophils in the brain. Overall, both biomarkers are important players of the innate immunity. Our results are encouraging evidence that inflammatory processes are activated in MCI patients, although they only give a snapshot of all processes involved at a given moment. This certainly reflects the heterogeneity and complexity associated with Alzheimer's disease continuum
