Soluble TREM2 changes during the clinical course of Alzheimer's disease: A meta-analysis

Neurosci Lett. 2018 Nov 1:686:10-16. doi: 10.1016/j.neulet.2018.08.038. Epub 2018 Aug 29.

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.

Keywords: Alzheimer’s disease; Inflammation; Meta-analysis; Soluble TREM2.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / drug therapy*
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Biomarkers / cerebrospinal fluid
  • Case-Control Studies
  • Cognitive Dysfunction / cerebrospinal fluid
  • Cognitive Dysfunction / drug therapy
  • Disease Progression
  • Humans
  • Membrane Glycoproteins / cerebrospinal fluid*
  • Peptide Fragments / cerebrospinal fluid
  • Receptors, Immunologic
  • tau Proteins / cerebrospinal fluid

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • Membrane Glycoproteins
  • Peptide Fragments
  • Receptors, Immunologic
  • TREM2 protein, human
  • tau Proteins