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Soluble TREM2 changes during the clinical course of Alzheimer's disease: A meta-analysis
Dan Liu1, Bing Cao2, Yujia Zhao2
1Department of Occupational and Environmental Health Sciences, Peking University, Beijing, 100191, China; Population Health Sciences, German Center for Neurodegenerative diseases (DNZE), Bonn, Germany.
Abstract:
Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) is a potential and novel biomarker of neuroinflammation implicated in the onset and progression of Alzheimer's disease (AD). However, previous studies evaluating levels of sTREM2 in different clinical stages of AD have yielded inconsistent results. To clarify the dynamic change of sTREM2 in AD progression, we conducted a meta-analysis of case-control and cohort studies to determine the role of cerebral spinal fluid (CSF) and plasma sTREM2 levels in preclinical AD (pre-AD), mild cognitive impairment (MCI) and AD dementia. We searched PubMed, MEDLINE, EMBASE, the Cochrane Library for English articles and Sinomed, CNKI for Chinese. The associations between sTREM2 levels and AD continuum groups (pre-AD, MCI and AD) were analyzed. We further performed detailed subgroup analysis and meta-regression to detect the sources of heterogeneity. 17 reports comprising 82 patients with pre-AD, 159 with MCI, 598 with AD, as well as 754 controls were included in this analysis. Regarding the sTREM2 levels in CSF, the overall pooled standard mean difference (SMD) revealed significantly elevated sTREM2 levels in the whole AD continuum groups (SMD = 0.48; 95% CI: 0.23, 0.73; P < 0.001) compared with controls. The levels of sTREM2 significantly increased in pre-AD (SMD = 0.47; 95% CI: 0.21, 0.73; P < 0.001), the highest increase occurred in MCI group (SMD = 0.77; 95% CI: -0.05, 1.59; P = 0.066), and the effect size of AD group (SMD = 0.39; 95% CI: 0.13, 0.65; P = 0.004) was also higher compared with control. However, for sTREM2 levels measured in plasma, no significant differences were found (SMD = 0.11; 95% CI: -0.06, 0.27; P = 0.217). Therefore, our study showed that sTREM2 levels increased in the earlier course of AD, and slightly attenuated in dementia stage. The current results indicated that sTREM2 levels fluctuate as a function of clinical stage in AD and it might be a novel inflammatory biomarker involved in different stages of AD.
Insights
Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) levels in cerebrospinal fluid increase during early Alzheimer's disease stages, peaking in mild cognitive impairment. Plasma sTREM2 levels showed no significant changes, suggesting CSF sTREM2 is a dynamic biomarker for AD progression.
Area of Science:
- Neuroscience
- Biomarker Discovery
- Neuroinflammation
Background:
- Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) is a novel biomarker for neuroinflammation in Alzheimer's disease (AD).
- Previous studies on sTREM2 levels in AD progression have shown inconsistent results.
- Clarifying the dynamic changes of sTREM2 is crucial for understanding its role in AD.
Purpose of the Study:
- To conduct a meta-analysis evaluating cerebrospinal fluid (CSF) and plasma sTREM2 levels across the Alzheimer's disease continuum.
- To determine the role of sTREM2 in preclinical AD (pre-AD), mild cognitive impairment (MCI), and AD dementia.
Main Methods:
- Meta-analysis of case-control and cohort studies.
- Searched PubMed, MEDLINE, EMBASE, Cochrane Library, Sinomed, and CNKI.
- Analyzed associations between sTREM2 levels and AD continuum groups (pre-AD, MCI, AD) versus controls.
- Performed subgroup analysis and meta-regression to identify heterogeneity sources.
Main Results:
- Included 17 reports with 82 pre-AD, 159 MCI, 598 AD patients, and 754 controls.
- Significantly elevated CSF sTREM2 levels were found across the AD continuum (SMD = 0.48, P < 0.001).
- CSF sTREM2 increased in pre-AD (SMD = 0.47), peaked in MCI (SMD = 0.77), and remained elevated in AD dementia (SMD = 0.39).
- No significant differences in plasma sTREM2 levels were observed (SMD = 0.11, P = 0.217).
Conclusions:
- CSF sTREM2 levels increase during the early stages of AD, particularly in MCI, and slightly decrease in the dementia stage.
- CSF sTREM2 demonstrates dynamic changes correlating with clinical stage in AD.
- CSF sTREM2 may serve as a novel inflammatory biomarker for different stages of Alzheimer's disease.