Soluble TREM2 levels associate with conversion from mild cognitive impairment to Alzheimer?s disease

BACKGROUND. Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) plays an important role in the clearance of pathological amyloid-beta (A beta) in Alzheimer's disease (AD). This study aimed to explore sTREM2 as a central and peripheral predictor of the conversion from mild cognitive impairment (MCI) to AD. METHODS. sTREM2 and A beta 1-42 levels in cerebrospinal fluid (CSF) and florbetapir-PET (AV45) images were analyzed for healthy control (HCs), patients with MCI, and patients with AD from the ADNI database. Peripheral plasma sTREM2 and A beta 1-42 levels were determined for our Neurology database of Ruijin Hospital for Alzheimer's Disease (NRHAD) cohort, and patients with MCI were reevaluated at follow-up visits to assess for progression to AD. The association between CSF and plasma sTREM2 levels was analyzed in data from the Chinese Alzheimer's Biomarker and Lifestyle (CABLE) database.RESULTS. The results showed that patients with MCI who had low levels of CSF sTREM2 and A beta 1-42 were more likely to develop AD. Among participants with positive A beta deposition, as assessed by AV45 imaging, elevated CSF sTREM2 levels were associated with a decreased risk of MCI-to-AD conversion. Meanwhile, in the NRHAD cohort, individuals in the MCI group with high sTREM2 levels in plasma were at a greater risk for AD, whereas low A beta 1-42 with high sTREM2 levels in plasma were associated with a faster cognitive decline. In addition, CSF sTREM2 levels were highly correlated with plasma sTREM2 levels in the CABLE database.CONCLUSION. These findings suggest that sTREM2 may be useful as a potential predictive biomarker of MCI-to-AD conversion.

Automated summary

This study found that sTREM2 may serve as a potential predictive biomarker of the conversion from MCI to AD. Low levels of CSF sTREM2 and Aβ1-42 were associated with an increased risk of MCI-to-AD conversion, while elevated CSF sTREM2 levels were associated with a decreased risk. In the NRHAD cohort, individuals in the MCI group with high plasma sTREM2 levels were more likely to progress to AD, and those with low Aβ1-42 and high plasma sTREM2 levels had a faster cognitive decline. CSF sTREM2 levels were highly correlated with plasma sTREM2 levels in the CABLE database.