Cerebrospinal fluid sTREM2 in Alzheimer\u2019s disease: comparisons between clinical presentation and AT classification

Anne-Brita Knapskog,Lars N G Nilsson,Ingvild Saltvedt,Knut Engedal,Karin Persson,Leiv Otto Watne,Kristi Henjum,Ane-Victoria Idland,Rannveig Sakshaug Eldholm

doi:10.1038/s41598-020-72878-8

Abstract

Triggering receptor expressed on myeloid cells 2 (TREM2) is an innate immune receptor expressed by microglia. Its cleaved fragments, soluble TREM2 (sTREM2), can be measured in the cerebrospinal fluid (CSF). Previous studies indicate higher CSF sTREM2 in symptomatic AD; however most of these studies have included biomarker positive AD cases and biomarker negative controls. The aim of the study was to explore potential differences in the CSF level of sTREM2 and factors associated with an increased sTREM2 level in patients diagnosed with mild cognitive impairment (MCI) or dementia due to AD compared with cognitively unimpaired controls as judged by clinical symptoms and biomarker category (AT). We included 299 memory clinic patients, 62 (20.7%) with AD-MCI and 237 (79.3%) with AD dementia, and 113 cognitively unimpaired controls. CSF measures of the core biomarkers were applied to determine AT status. CSF sTREM2 was analyzed by ELISA. Patients presented with comparable CSF sTREM2 levels as the cognitively unimpaired (9.6 ng/ml [SD 4.7] versus 8.8 ng/ml [SD 3.6], p = 0.27). We found that CSF sTREM2 associated with age-related neuroinflammation and tauopathy irrespectively of amyloid β, APOE ε4 status or gender. The findings were similar in both symptomatic and non-symptomatic individuals.

Highlights

Triggering receptor expressed on myeloid cells 2 (TREM2) is an innate immune receptor expressed by microglia
By including a relatively large number of patients referred to two memory clinics for a diagnostic workup and cognitively unimpaired controls, we aimed to explore potential differences in soluble TREM2 (sTREM2) levels in patients clinically diagnosed with Alzheimer’s disease (AD) at mild cognitive impairment (MCI) or dementia stage relative to cognitively unimpaired, and the differences across and within these groups when defined by AT(N) category
Of the 299 memory clinic patients, 62 (20.7%) were clinically diagnosed with MCI due to AD and 237 (79.3%) patients with dementia due to AD, whereas 11 (17.7%) AD-MCI and 59 (24.9%) AD dementia patients had AD mixed with cerebrovascular disease

Summary

Introduction

Triggering receptor expressed on myeloid cells 2 (TREM2) is an innate immune receptor expressed by microglia. The aim of the study was to explore potential differences in the CSF level of sTREM2 and factors associated with an increased sTREM2 level in patients diagnosed with mild cognitive impairment (MCI) or dementia due to AD compared with cognitively unimpaired controls as judged by clinical symptoms and biomarker category (AT). We found that CSF sTREM2 associated with age-related neuroinflammation and tauopathy irrespectively of amyloid β, APOE ε4 status or gender. Abbreviations A Amyloid pathology Aβ42 Amyloid β1-42 AD Alzheimer’s disease CSF Cerebrospinal fluid MCI Mild cognitive impairment MMSE Mini mental status examination N Neurodegeneration PART Primary age-related tauopathy P-tau Phosphorylated tau SNAP Suspected non-Alzheimer disease pathophysiology sTREM2 Soluble triggering receptor expressed on myeloid cells 2 T Phosphorylated tau pathology T-tau Total tau Scientific Reports | (2020) 10:15886. Genetic linkage of TREM2 variants to other dementias reinforces the importance of TREM2-function for cognitively normal a ging[13,14]

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