The Emerging Roles and Therapeutic Potential of Soluble TREM2 in Alzheimer’s Disease
Alzheimer’s disease (AD) is the most common form of dementia characterized by the deposition of extracellular amyloid-β (Aβ)-containing plaques, the formation of intraneuronal neurofibrillary tangles as well as neuroinflammatory changes. As the key player in the brain innate immune system, microglia...
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doaj-b109aa706a624a3c999ff4d34d5c30db2020-11-25T01:58:23ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652019-11-011110.3389/fnagi.2019.00328507055The Emerging Roles and Therapeutic Potential of Soluble TREM2 in Alzheimer’s DiseaseLi Zhong0Xiao-Fen Chen1Xiao-Fen Chen2Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, Medical College, Xiamen University, Xiamen, ChinaFujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, Medical College, Xiamen University, Xiamen, ChinaShenzhen Research Institute of Xiamen University, Shenzhen, ChinaAlzheimer’s disease (AD) is the most common form of dementia characterized by the deposition of extracellular amyloid-β (Aβ)-containing plaques, the formation of intraneuronal neurofibrillary tangles as well as neuroinflammatory changes. As the key player in the brain innate immune system, microglia has now taken a center stage in AD research. A large number of AD risk loci identified by genome-wide association studies are located in or near the genes highly expressed in microglia. Among them, the triggering receptor expressed on myeloid cells 2 (TREM2) has drawn much attention. A rare variant in TREM2 increases AD risk with an odds ratio comparable to the strongest genetic risk factor apolipoprotein ε4 allele. In the past 6 years, extensive studies have dissected the mechanisms by which TREM2 and its variants modulate microglial functions impacting amyloid and tau pathologies in both animal models and human studies. In addition to the full-length TREM2, research on the soluble form of TREM2 (sTREM2) has facilitated the translation of preclinical findings on TREM2. In this review, we summarize our current understanding of the biology and pathobiology of sTREM2 including its origin, its emergence as a disease biomarker, and its potential neuroprotective functions. These aspects are important for understanding the involvement of sTREM2 in AD pathogenesis and may provide novel insights into applying sTREM2 for AD diagnosis and therapy.https://www.frontiersin.org/article/10.3389/fnagi.2019.00328/fullAlzheimer’s diseasemicrogliasoluble TREM2biomarkerneuroinflammation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Li Zhong Xiao-Fen Chen Xiao-Fen Chen |
spellingShingle |
Li Zhong Xiao-Fen Chen Xiao-Fen Chen The Emerging Roles and Therapeutic Potential of Soluble TREM2 in Alzheimer’s Disease Frontiers in Aging Neuroscience Alzheimer’s disease microglia soluble TREM2 biomarker neuroinflammation |
author_facet |
Li Zhong Xiao-Fen Chen Xiao-Fen Chen |
author_sort |
Li Zhong |
title |
The Emerging Roles and Therapeutic Potential of Soluble TREM2 in Alzheimer’s Disease |
title_short |
The Emerging Roles and Therapeutic Potential of Soluble TREM2 in Alzheimer’s Disease |
title_full |
The Emerging Roles and Therapeutic Potential of Soluble TREM2 in Alzheimer’s Disease |
title_fullStr |
The Emerging Roles and Therapeutic Potential of Soluble TREM2 in Alzheimer’s Disease |
title_full_unstemmed |
The Emerging Roles and Therapeutic Potential of Soluble TREM2 in Alzheimer’s Disease |
title_sort |
emerging roles and therapeutic potential of soluble trem2 in alzheimer’s disease |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Aging Neuroscience |
issn |
1663-4365 |
publishDate |
2019-11-01 |
description |
Alzheimer’s disease (AD) is the most common form of dementia characterized by the deposition of extracellular amyloid-β (Aβ)-containing plaques, the formation of intraneuronal neurofibrillary tangles as well as neuroinflammatory changes. As the key player in the brain innate immune system, microglia has now taken a center stage in AD research. A large number of AD risk loci identified by genome-wide association studies are located in or near the genes highly expressed in microglia. Among them, the triggering receptor expressed on myeloid cells 2 (TREM2) has drawn much attention. A rare variant in TREM2 increases AD risk with an odds ratio comparable to the strongest genetic risk factor apolipoprotein ε4 allele. In the past 6 years, extensive studies have dissected the mechanisms by which TREM2 and its variants modulate microglial functions impacting amyloid and tau pathologies in both animal models and human studies. In addition to the full-length TREM2, research on the soluble form of TREM2 (sTREM2) has facilitated the translation of preclinical findings on TREM2. In this review, we summarize our current understanding of the biology and pathobiology of sTREM2 including its origin, its emergence as a disease biomarker, and its potential neuroprotective functions. These aspects are important for understanding the involvement of sTREM2 in AD pathogenesis and may provide novel insights into applying sTREM2 for AD diagnosis and therapy. |
topic |
Alzheimer’s disease microglia soluble TREM2 biomarker neuroinflammation |
url |
https://www.frontiersin.org/article/10.3389/fnagi.2019.00328/full |
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