TREM2 enables amyloid β clearance by microglia

Rivest, Serge

doi:10.1038/cr.2015.37

Cited by 29 publications

(20 citation statements)

References 6 publications

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“…However, the implication of the cerebral Aβ reduction on cognition has not been addressed, thus the functional outcome of the here above reported observations cannot be assessed (Rivest, 2015). Nonetheless, the role of TREM2 seems very complex.…”

Section: A) Microglia Reported Contribution In Ad Attenuationmentioning

confidence: 58%

Microglia in Alzheimer’s disease: A multifaceted relationship

ElAli

Rivest

2016

Brain, Behavior, and Immunity

Self Cite

106

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Section: A) Microglia Reported Contribution In Ad Attenuationmentioning

confidence: 58%

Microglia in Alzheimer’s disease: A multifaceted relationship

ElAli

Rivest

2016

Brain, Behavior, and Immunity

Self Cite

106

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“…). Recently, TREM2 has emerged as an important immunomodulatory molecule that is crucial for clearance of extracellular protein aggregates such as Aβ (Rivest ; Wang et al . ; Yeh et al .…”

Section: Discussionmentioning

confidence: 99%

“…Hence, the effects of reduced TREM2 on the autophagy pathway and Aβ accumulation in brains of HIV+ individuals warrant future investigation. Recently, multiple studies using cellular and transgenic animal models support a role for TREM2 to detect Aβ, facilitating clearance of damaged cells and protein aggregates, and moderating the immune response (Rivest ; Wang et al . ; Yeh et al .…”

Section: Discussionmentioning

confidence: 99%

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Alterations in brain TREM2 and Amyloid‐β levels are associated with neurocognitive impairment in HIV‐infected persons on antiretroviral therapy

Fields

Spencer

Swinton

et al. 2018

Journal of Neurochemistry

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Neuroinflammation is a common pathological correlate of HIV-associated neurocognitive disorders (HAND) in individuals on antiretroviral therapy (ART). Triggering receptor expressed on myeloid cells 2 (TREM2) regulates neuroinflammation, clears extracellular Amyloid (A)-β, surveys for damaged neurons, and orchestrates microglial differentiation. TREM2 has not been studied in HIV+ brain tissues. In this retrospective study, we investigated TREM2 expression levels and localization to microglia, Aβ protein levels, and tumor necrosis factor (TNF)-α transcript levels in the frontal cortices of 52 HIV+ decedents. All donors had been on ART; 14 were cognitively normal (CN), 17 had an asymptomatic neurocognitive impairment (ANI), and 21 had a minor neurocognitive disorder (MND). Total TREM2 protein levels were increased in the soluble and decreased in the membrane-enriched fractions of MND brain tissues compared to CN; however, brains from MND Hispanics showed the most robust alterations in TREM2 as well as significantly increased TNF-α mRNA and Aβ levels when compared to CN Hispanics. Significant alterations in the expression of total TREM2 protein and transcripts for TNF-α were not observed in non-Hispanics, despite higher levels of Aβ in the non-Hispanic CN group compared to the non-Hispanic MND groups. These findings show that decreased and increased TREM2 in membrane-bound fractions and in soluble-enriched fractions, respectively, is associated with increased Aβ and neuroinflammation in this cohort of HIV+ brains, particularly those identifying as Hispanics. These findings suggest a role for TREM2 in the brain of HIV+ individuals may deserve more investigation as a biomarker for HAND and as a possible therapeutic target. Open Data: Materials are available on https://cos.io/our-services/open-science-badges/ https://osf.io/93n6m/.

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“…TREM2 is a newly discovered gene that is associated with an increased risk of AD (Guerreiro et al 2013, Jin et al 2014). TREM2 is a transmembrane protein that is expressed on microglia in the brain and can regulate microglial functions such as phagocytosis and inflammatory reactivity (Hsieh et al 2009, Rivest 2015). However, very little is known about the mechanisms by which TREM2 variants can increase the risk to develop AD.…”

Section: Sex Differences In Brain Disorders (Human Clinical Studies)mentioning

confidence: 99%

Sex differences in neurodevelopmental and neurodegenerative disorders: Focus on microglial function and neuroinflammation during development

Hanamsagar

Bilbo

2016

The Journal of Steroid Biochemistry and Molecular Biology

307

208

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Several neurological conditions are associated with sex differences in prevalence or outcome. For example, autism predominantly affects boys, depression is more common in women, Parkinson's disease more common in men, and Multiple sclerosis in women. In the case of stroke, women have a less favorable outcome and suffer from a more precipitous drop in health status compared to men. As a result, treatment of such diseases is difficult and yields variable results. Despite this, sex is rarely considered when making treatment decisions. The mechanisms underlying sex differences in disease progression are not well understood, however a strong link exists between different inflammation states of men and women and their propensity to develop certain diseases. As neuroinflammation is an important component of pathophysiology in many neurological conditions, it can be speculated that any changes in the state of inflammation in the brain during normal development can potentially lead to an increase in susceptibility to neurological and neurodegenerative diseases. Microglia play a crucial role in onset and modulation of inflammation and thus sex differences in microglial function could explain, at least in part, differences observed in susceptibilities and outcomes of neurological disorders in men and women. Understanding the mechanisms behind sex differences could help develop more targeted therapy with higher success rate, especially in diseases where sex differences are most prominent.

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TREM2 enables amyloid β clearance by microglia

Cited by 29 publications

References 6 publications

Microglia in Alzheimer’s disease: A multifaceted relationship

Microglia in Alzheimer’s disease: A multifaceted relationship

Alterations in brain TREM2 and Amyloid‐β levels are associated with neurocognitive impairment in HIV‐infected persons on antiretroviral therapy

Sex differences in neurodevelopmental and neurodegenerative disorders: Focus on microglial function and neuroinflammation during development

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