TREM2: Modulator of Lipid Metabolism in Microglia

Damisah, Eyiyemisi; Rai, Anupama; Grutzendler, Jaime

doi:10.1016/j.neuron.2020.02.008

Cited by 37 publications

(30 citation statements)

References 10 publications

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“…TREM2 has also been demonstrated to regulate lipid metabolism in microglia. In a cuprizoneinduced demyelination model, TREM2-deficient microglia failed to digest myelin lipid (Cantoni et al, 2015;Damisah et al, 2020;Nugent et al, 2020). Single cell RNA-seq analysis further showed that the transcriptional programs related to lysosomal degradative and cholesterol transport were failed in TREM2 deficient microglia (Nugent et al, 2020).…”

Section: Trem2 In Alsmentioning

confidence: 99%

Microglial TREM2 in amyotrophic lateral sclerosis

Xie

Zhao

Bosco

et al. 2021

Developmental Neurobiology

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Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is an aggressive motor neuron degenerative disease characterized by selective loss of both upper and lower motor neurons. The mechanisms underlying disease initiation and progression are poorly understood. The involvement of nonmotor neuraxis emphasizes the contribution of glial cells in disease progress. Microglia comprise a unique subset of glial cells and are the principal immune cells in the central nervous system (CNS). Triggering receptor expressed on myeloid cell 2 (TREM2) is a surface receptor that, within the CNS, is exclusively expressed on microglia and plays crucial roles in microglial proliferation, migration, activation, metabolism, and phagocytosis. Genetic evidence has linked TREM2 to neurodegenerative diseases including ALS, but its function in ALS pathogenesis is largely unknown. In this review, we summarize how microglial activation, with a specific focus on TREM2 function, affects ALS progression clinically and experimentally. Understanding microglial TREM2 function will help pinpoint the molecular target for ALS treatment.

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Section: Trem2 In Alsmentioning

confidence: 99%

Microglial TREM2 in amyotrophic lateral sclerosis

Xie

Zhao

Bosco

et al. 2021

Developmental Neurobiology

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“…The role of sTREM2 in AD is contentious 2 , 6 , 15 – 17 . It could be either a byproduct of full-length TREM2 shedding or an active peptide playing a role in microglial modulation 18 , 19 . The increase in CSF sTREM2 levels in the early symptomatic stage of AD was interpreted to reflect a corresponding change in status of microglial activation in response to neurodegeneration induced by hyperphosphorylated tau aggregation 8 .…”

Section: Discussionmentioning

confidence: 99%

The relationship of soluble TREM2 to other biomarkers of sporadic Alzheimer’s disease

Park

Lee

Kim

et al. 2021

Sci Rep

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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.

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“…The role of sTREM2 in AD is contentious [2,6,[15][16][17] . It could be either a byproduct of full-length TREM2 shedding or an active peptide playing a role in microglial modulation [18,19] . The increase in CSF sTREM2 levels in the early symptomatic stage of AD was interpreted to re ect a corresponding change in status of microglial activation in response to neurodegeneration induced by hyperphosphorylated tau aggregation [8] .…”

Section: Discussionmentioning

confidence: 99%

The Relationship of Soluble TREM2 to Other Biomarkers of Sporadic Alzheimer’s Disease

Park

Lee

Kim

et al. 2021

Preprint

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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.

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TREM2: Modulator of Lipid Metabolism in Microglia

Cited by 37 publications

References 10 publications

Microglial TREM2 in amyotrophic lateral sclerosis

Microglial TREM2 in amyotrophic lateral sclerosis

The relationship of soluble TREM2 to other biomarkers of sporadic Alzheimer’s disease

The Relationship of Soluble TREM2 to Other Biomarkers of Sporadic Alzheimer’s Disease

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