Role of TREM2 in Alzheimer's Disease and its Consequences on β- Amyloid, Tau and Neurofibrillary Tangles

Singh, Anurag; Mishra, Gaurav; Maurya, Anand Kumar; Awasthi, Rajendra; Kumari, K Meena; Thakur, Abhimanyu; Rai, Anshul; Kumar, Gagan; Sharma, Bhupesh; Kulkarni, Giriraj T.; Singh, Santosh Kumar

doi:10.2174/1567205016666190903102822

Cited by 38 publications

(22 citation statements)

References 95 publications

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“…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 . Another cross-sectional study of sporadic AD patients showed that the levels of sTREM2 peaked at the early symptomatic phase of the disease and that the CSF sTREM2 levels were positively correlated with the concentrations of T-tau and P-tau in the CSF, suggesting the important role of sTREM2 in the development of AD pathology and neurodegeneration 9 , 20 , 21 . We can suggest that elevated levels of sTREM2 may have close relationship to inducing tau phosphorylation in neurites neighboring amyloid plaques 22 , 23 .…”

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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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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“…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] . Another cross-sectional study of sporadic AD patients showed that the levels of sTREM2 peaked at the early symptomatic phase of the disease and that the CSF sTREM2 levels were positively correlated with the concentrations of T-tau and P-tau in the CSF, suggesting the important role of sTREM2 in the development of AD pathology and neurodegeneration [9,20,21] . We can speculate that elevated levels of sTREM2 may be responsible for inducing tau phosphorylation in neurites neighboring amyloid plaques [22,23] .…”

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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“…Besides, a negative correlation between the concentration of TREM2 and tau fibrils was identified in the putamen of DLB cases, and CSF soluble TREM2 has been clarified as highly associated with total tau and NFT densities (phosphorylated tau) [69]. The possible mechanism of TREM2 associated tau pathology is disturbing the contact between microglia and neurons and affecting the pathological spread of tau [70].…”

Section: Interaction Of Reactive Oxygen Species and Microglia In The mentioning

confidence: 95%

Microglia Implicated in Tauopathy in the Striatum of Neurodegenerative Disease Patients from Genotype to Phenotype

Knight

Yang

et al. 2020

IJMS

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We found interactions between dopamine and oxidative damage in the striatum involved in advanced neurodegeneration, which probably change the microglial phenotype. We observed possible microglia dystrophy in the striatum of neurodegenerative brains. To investigate the interactions between oxidative damage and microglial phenotype, we quantified myeloperoxidase (MPO), poly (ADP-Ribose) (PAR), and triggering receptors expressed on myeloid cell 2 (TREM2) using enzyme-linked immunosorbent assay (ELISA). To test the correlations of microglia dystrophy and tauopathy, we quantified translocator protein (TSPO) and tau fibrils using autoradiography. We chose the caudate and putamen of Lewy body diseases (LBDs) (Parkinson’s disease, Parkinson’s disease dementia, and Dementia with Lewy body), Alzheimer’s disease (AD), and control brains and genotyped for TSPO, TREM2, and bridging integrator 1 (BIN1) genes using single nucleotide polymorphisms (SNP) assays. TREM2 gene variants were absent across all samples. However, associations between TSPO and BIN1 gene polymorphisms and TSPO, MPO, TREM2, and PAR level variations were found. PAR levels reduced significantly in the caudate of LBDs. TSPO density and tau fibrils decreased remarkably in the striatum of LBDs but increased in AD. Oxidative damage, induced by misfolded tau proteins and dopamine metabolism, causes microglia dystrophy or senescence during the late stage of LBDs. Consequently, microglia dysfunction conversely reduces tau propagation. The G allele of the BIN1 gene is a potential risk factor for tauopathy.

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Role of TREM2 in Alzheimer's Disease and its Consequences on β- Amyloid, Tau and Neurofibrillary Tangles

Cited by 38 publications

References 95 publications

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

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

Microglia Implicated in Tauopathy in the Striatum of Neurodegenerative Disease Patients from Genotype to Phenotype

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