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Soluble TREM2 and Inflammatory Proteins in Alzheimer's Disease Cerebrospinal Fluid
Boris-Stephan Rauchmann1,2, Angélique Sadlon3, Robert Perneczky2,3,4,5
1Department of Radiology, University Hospital, LMU Munich, Germany.
Abstract:
The present study explores the associations of soluble TREM2, an important regulator of microglial activity linked to Alzheimer's disease (AD), with other known inflammatory proteins in cerebrospinal fluid (CSF). We studied 303 participants, including 89 controls, 135 mild cognitive impairment, and 79 AD dementia patients. Using established CSF biomarkers, subjects were classified according to the National Institute on Aging-Alzheimer's Association research framework, which groups markers into those of amyloid-β deposition (A), tau pathology (T), and neurodegeneration (N). TNFR1, TNFR2, TGF-β1, TGFβ2, IL-9, TNF-α, ICAM1, and VCAM1 showed significant concentration differences between the ATN groups, with higher concentrations in more advanced disease categories. sTREM2 was positively associated with the pro-inflammatory proteins TNF-α, TNFR1, TNFR2, ICAM1, VCAM1, and IP-10 and negatively with IL-21; also, positive associations with the anti-inflammatory proteins TGFβ1, IL-10, and IL-9 were found. Pathway enrichment analysis highlighted the involvement of sTREM2 in key functional clusters including immunoglobulin and cytokine production and cellular response to lipopolysaccharides, cytokines, and steroid hormones. Our work provides further evidence in support of TREM2 as amarker of neuroinflammatory response in AD.
Insights
Soluble TREM2 (sTREM2) in cerebrospinal fluid is linked to inflammatory proteins in Alzheimer's disease (AD). Higher sTREM2 levels correlate with specific inflammatory markers, suggesting its role in neuroinflammation during AD progression.
Area of Science:
- Neuroscience
- Immunology
- Biochemistry
Background:
- Soluble TREM2 (sTREM2) is a key regulator of microglial activity and is implicated in Alzheimer's disease (AD).
- Understanding the relationship between sTREM2 and other inflammatory proteins in cerebrospinal fluid (CSF) is crucial for elucidating AD pathogenesis.
- Existing research highlights the involvement of neuroinflammation in AD progression.
Purpose of the Study:
- To investigate the associations between sTREM2 and various inflammatory proteins in the CSF of individuals across the AD spectrum.
- To determine how these associations relate to established Alzheimer's disease biomarkers (amyloid-β, tau, neurodegeneration).
- To explore the functional pathways linked to sTREM2 in the context of neuroinflammation.
Main Methods:
- Analysis of CSF samples from 303 participants (controls, mild cognitive impairment, AD dementia).
- Classification of participants using the National Institute on Aging-Alzheimer's Association research framework (ATN).
- Measurement of sTREM2 and other inflammatory protein concentrations (e.g., TNFR1, TNFR2, TGF-β1, TNF-α, ICAM1, VCAM1, IL-9, IP-10, IL-10, IL-21) and pathway enrichment analysis.
Main Results:
- Significant concentration differences in several inflammatory proteins (TNFR1, TNFR2, TGF-β1, TGFβ2, IL-9, TNF-α, ICAM1, VCAM1) were observed across ATN groups, increasing with disease severity.
- sTREM2 showed positive associations with pro-inflammatory proteins (TNF-α, TNFR1, TNFR2, ICAM1, VCAM1, IP-10) and anti-inflammatory proteins (TGFβ1, IL-10, IL-9).
- Pathway analysis indicated sTREM2 involvement in immunoglobulin and cytokine production, and cellular responses to lipopolysaccharides, cytokines, and steroid hormones.
Conclusions:
- sTREM2 is associated with a broad range of inflammatory proteins in CSF, reflecting its role in the neuroinflammatory response in Alzheimer's disease.
- These findings support TREM2's utility as a biomarker for neuroinflammation in AD.
- The study provides further evidence for the complex interplay between TREM2, microglial function, and inflammatory processes in AD pathogenesis.
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