The relationship of soluble TREM2 to other biomarkers of sporadic Alzheimer\u2019s disease

So-Hee Park,Hyung-Ji Kim,Hyun-Hee Park,Jae-Hong Lee,Sunju Lee,Seong-Ho Koh,Eun-Hye Lee,Sang Won Seo,Sungyang Jo

doi:10.1038/s41598-021-92101-6

Abstract

Microglial activation is a central player in the pathophysiology of Alzheimer’s disease (AD). The soluble fragment of triggering receptor expressed on myeloid cells 2 (sTREM2) can serve as a marker for microglial activation and has been shown to be overexpressed in AD. However, the relationship of sTREM2 with other AD biomarkers has not been extensively studied. We investigated the relationship between cerebrospinal fluid (CSF) sTREM2 and other AD biomarkers and examined the correlation of plasma sTREM2 with CSF sTREM2 in a cohort of individuals with AD and without AD. Participants were consecutively recruited from Asan Medical Center from 2018 to 2020. Subjects were stratified by their amyloid positivity and clinical status. Along with other AD biomarkers, sTREM2 level was measured in the plasma as well as CSF. In 101 patients with either amyloid-positive or negative status, CSF sTREM2 was closely associated with CSF T-tau and P-tau and not with Abeta42. CSF sTREM2 levels were found to be strongly correlated with CSF neurofilament light chain. The comparison of CSF and plasma sTREM2 levels tended to have an inverse correlation. Plasma sTREM2 and P-tau levels were oppositely influenced by age. Our results suggest that neuroinflammation may be closely associated with tau-induced neurodegeneration.

Highlights

Biomarkers have become an essential component of Alzheimer’s research
If soluble fragment of triggering receptor expressed on myeloid cells 2 (TREM2) (sTREM2)-induced changes in the brain can be reflected in the plasma levels of sTREM2 akin to neurofilament light chain in multiple sclerosis, we will be able to elucidate neuroinflammation associated with Alzheimer’s disease (AD) throughout the course of the disease
The major findings of this study were as follows: first, we observed that cerebrospinal fluid (CSF) sTREM2 was closely associated with CSF T-tau and P-tau, but not so much with Aβ42; second, the CSF sTREM2 levels were found to be strongly correlated with CSF neurofilament light chain (NfL); third, comparison of the CSF sTREM2 and plasma sTREM2 levels tended to show an inverse correlation; fourth, the plasma sTREM2 and P-tau levels were influenced by age in an opposite way

Summary

Introduction

Extracellular amyloid plaque and intraneuronal hyperphosphorylated tau accumulation are considered hallmarks of Alzheimer’s disease (AD) and many biomarkers have been developed to reflect these central pathophysiological events. By virtue of these biomarkers, we possess a valuable window into the changes occurring in the brain of individuals with Alzheimer’s disease and can identify the disease process at the earliest possible s tage[1]. Neuroinflammation has been deemed a secondary phenomenon, but is emerging as a central player in the development of A D2–4 This theory is centered on microglial activation, which can be brought about by various stimuli, including beta-amyloid. The purpose of this study was to investigate the relationship between CSF sTREM2 and other AD biomarkers and to examine the plasma levels of sTREM2 and its correlation with CSF sTREM2 in a cohort population of AD and non-AD conditions

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Conclusion