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PET Imaging of Neuroinflammation Using [11C]DPA-713 in a Mouse Model of Ischemic Stroke
Published on: June 14, 2018
Soluble Triggering Receptor Expressed on Myeloid Cells 2 as a Promising Biomarker for Poststroke Depression After
Ming Wang1, Jiayi Long1, Ke Yuan1
1Department of Epidemiology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology Suzhou Medical College of Soochow University Suzhou China.
Background:
Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) was reported to induce inflammatory responses, enhance microglial survival, and contribute to the development of neurodegenerative disorders. We aimed to prospectively investigate the association between plasma sTREM2 levels and poststroke depression (PSD).
Methods:
We measured plasma sTREM2 levels in 590 patients with ischemic stroke from 7 participating hospitals of the CATIS (China Antihypertensive Trial in Acute Ischemic Stroke) trial. The 24-item Hamilton Rating Scale for Depression was used to assess depression at 3 months after ischemic stroke onset, and PSD was defined as a score of ≥8. The predictive performance of sTREM2 was evaluated by calculating the net reclassification index and integrated discrimination improvement. Random forest regression model was used to assess the importance of sTREM2, clinical variables, and other potential biomarkers.
Results:
Of the 590 participants, 229 (38.8%) patients experienced PSD. The multivariable-adjusted odds ratio for the highest quartile of sTREM2 compared with the lowest quartile was 1.98 (95% CI, 1.16-3.37) for PSD. Multiple adjusted spline regression analysis confirmed the linear dose-response relationship between sTREM2 levels and PSD (P for linearity=0.037). The addition of sTREM2 to the conventional risk factors model improved risk reclassification for PSD, as shown by a category-free net reclassification index of 19.3% (P=0.03) and integrated discrimination improvement of 1.1% (P=0.01). Furthermore, a random forest regression model suggested that sTREM2 was among the top 5 important indicators for PSD prediction.
Conclusions:
The present study demonstrated that elevated plasma sTREM2 levels were associated with an increased risk of PSD, suggesting that sTREM2 may be a promising prognostic biomarker for PSD.
Registration:
URL: https://clinicaltrials.gov; Unique identifier: NCT01840072.
Insights
Elevated plasma soluble triggering receptor expressed on myeloid cells 2 (sTREM2) levels are linked to a higher risk of poststroke depression (PSD). sTREM2 shows promise as a prognostic biomarker for predicting PSD after ischemic stroke.
Area of Science:
- Neuroscience
- Immunology
- Clinical Medicine
Background:
- Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) is implicated in neuroinflammation and microglial survival.
- sTREM2's role in neurodegenerative disorders is established.
- The association between sTREM2 and poststroke depression (PSD) remains to be prospectively investigated.
Purpose of the Study:
- To prospectively investigate the association between plasma sTREM2 levels and the incidence of poststroke depression (PSD).
Main Methods:
- Plasma sTREM2 levels were measured in 590 ischemic stroke patients from the CATIS trial.
- Depression was assessed using the 24-item Hamilton Rating Scale for Depression at 3 months post-stroke.
- Predictive performance was evaluated using net reclassification index and integrated discrimination improvement; random forest models identified key predictors.
Main Results:
- Poststroke depression (PSD) occurred in 38.8% of participants (229/590).
- Higher sTREM2 levels significantly correlated with increased PSD risk (OR 1.98; 95% CI, 1.16-3.37).
- sTREM2 improved PSD risk prediction models and was a top 5 predictor in random forest analysis.
Conclusions:
- Elevated plasma sTREM2 levels are associated with an increased risk of poststroke depression.
- sTREM2 may serve as a valuable prognostic biomarker for identifying patients at risk of PSD.
