The role of TREM2 in Alzheimer's disease and other neurodegenerative disorders

@article{Carmona2018TheRO,
  title={The role of TREM2 in Alzheimer's disease and other neurodegenerative disorders},
  author={Susana Carmona and Kathleen R Zahs and Elizabeth Wu and Kelly A. Dakin and Jose T Bras and Rita Guerreiro},
  journal={The Lancet Neurology},
  year={2018},
  volume={17},
  pages={721-730}
}
Role of TREM2 in Alzheimer's Disease: A Long Road Ahead.
TLDR
The role of soluble TREM2 as an effective biomarker and impending neuroprotection in AD is summarized and the strategies to develop therapeutic agents against T REM2 by employing its expression, function, and signalling pathways are focused on.
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The role of ubiquitin in neuronal homeostasis as well as in AD is discussed; crosstalks between the enzymes that regulate protein ubiquitination and the toxic proteins Tau and Aβ are summarized; emerging molecular mechanisms in AD are highlighted; and future strategies which aim to exploit the Ubiquitin system as a source for next-generation therapeutics are highlighted.
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TLDR
These genetic findings implicate the role of innate and adaptive immunity in LOAD pathogenesis and suggest that a systemic failure of cell-mediated amyloid-β (Aβ) clearance contributes to AD onset and progression.
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More extensive and more diverse genetic studies, as well as studies of deeply characterized families, will enhance the understanding of disease pathogenesis and put us on the correct path for the development of successful drugs.
The Other Side of Alzheimer’s Disease: Influence of Metabolic Disorder Features for Novel Diagnostic Biomarkers
TLDR
These findings revise the canonical understating of AD pathogenesis and suggest that AD has metabolic disorder features, and highlight the contribution of this novel understanding on the identification of new biomarkers for improving an early AD diagnosis.
Mitochondrial Dysfunction and Alzheimer’s Disease: Role of Microglia
TLDR
This chapter explores the role of mitochondrial dysfunction in microglia in case of AD and how understanding microglial physiology and mitochondrial dysfunction will enable better therapeutic interventions.
The Genetics of Alzheimer’s Disease in the Chinese Population
TLDR
Three early-onset AD causative genes (APP, PSEN1, and PSEN2) and some late-ONSet AD susceptibility genes and their mutation sites newly discovered in China are summarized and the potential mechanisms of these genetic susceptibilities in the pathogenesis of AD are introduced to help in understanding the genetic mechanisms underlying this devastating disease.
TREM2 Deficiency Disrupts Network Oscillations Leading to Epileptic Activity and Aggravates Amyloid-β-Related Hippocampal Pathophysiology in Mice.
TLDR
Findings indicate a role for TREM2-dependent microglial function in the hippocampal neuronal excitability in both wild type and Aβ overproducing mice, whereas deficiency in T REM2 function exacerbates disruptive effects of Aβ on hippocampal network oscillations.
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References

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TREM2 in neurodegeneration: evidence for association of the p.R47H variant with frontotemporal dementia and Parkinson’s disease
TLDR
The results suggest that the TREM2 p.R47H substitution is a risk factor for frontotemporal dementia and Parkinson's disease in addition to Alzheimer’s disease, and suggest a more general role for TREM 2 dysfunction in neurodegeneration, which could be related to its role in the immune response.
Identification of a rare coding variant in TREM2 in a Chinese individual with Alzheimer’s disease
TLDR
Evidence is provided that the A192T variant in TREM2 could contribute risk for Alzheimer’s disease and the importance of including diverse populations in research to identify genetic variation that contributes risk for AD and other neurodegenerative disorders.
TREM2 in Neurodegenerative Diseases
TLDR
A comprehensive review of the current understanding of T REM2 biology, including new insights into the regulation of TREM2 expression, and TREM1 signaling and function across NDDs, and the latest assessment of how these findings might be applied to immune-directed clinical biomarkers and therapeutics.
Disease Progression-Dependent Effects of TREM2 Deficiency in a Mouse Model of Alzheimer's Disease
TLDR
It is demonstrated that TREM2 deficiency ameliorates amyloid pathology early, but exacerbates it late in disease progression in the APPPS1–21 mouse model of AD, unifying previous work in the field and suggesting that T REM2 plays distinct functional roles at different stages in AD pathology.
Variant of TREM2 associated with the risk of Alzheimer's disease.
TLDR
These findings strongly implicate variant TREM2 in the pathogenesis of Alzheimer's disease and find that carriers of rs75932628-T between the ages of 80 and 100 years without Alzheimer’s disease had poorer cognitive function than noncarriers.
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TLDR
The expression of Aβ and phosphorylated tau (p-tau) in the frontal cortex and the hippocampus of five NHD cases were studied and several small Aβ-immunoreactive spheroids, almost undetectable in NHD brains were identified.
TREM2 variants: new keys to decipher Alzheimer disease pathogenesis
TLDR
How TREM2 may control the microglia response to Aβ and its impact on microglial senescence is discussed, as well as the interaction of TREM 2 with other molecules that are encoded by gene variants associated with AD and the hypothetical consequences of the cleavage of T REM2 from the cell surface.
R47H Variant of TREM2 Associated With Alzheimer Disease in a Large Late-Onset Family: Clinical, Genetic, and Neuropathological Study.
TLDR
The results demonstrate a complex genetic landscape of LOAD, even in a single pedigree with an apparent autosomal dominant pattern of inheritance and support the role of the TREM2 receptor in microglial clearance of aggregation-prone proteins that is in R47H carriers and may accelerate the course of disease.
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