Assessment of TREM2 rs75932628 association with Alzheimer's disease in a population-based sample: the Cache County Study

Murcia, Josue D. Gonzalez; Schmutz, Cameron; Munger, Caitlin; Perkes, Ammon; Gustin, Aaron; Peterson, Michael R.; Ebbert, Mark T. W.; Norton, Maria C.; Tschanz, JoAnn T.; Munger, Ronald G.; Corcoran, Christopher; Kauwe, John

doi:10.1016/j.neurobiolaging.2013.06.004

Cited by 48 publications

(32 citation statements)

References 11 publications

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“…The finding that TREM2 variants act as strong genetic risk factors for Alzheimer's disease and many other neurodegenerative diseases (Benitez, et al, 2013,Borroni, et al, 2014,Cady, et al, 2014,Giraldo, et al, 2013,Gonzalez Murcia, et al, 2013,R. Guerreiro, et al, 2013a,R.…”

Section: Discussionmentioning

confidence: 99%

“…These findings have spurred numerous studies addressing the association between TREM2 and AD and other neurodegenerative diseases. Although negatives have been reported (Jiao, et al, 2014,Miyashita, et al, 2014,Ruiz, et al, 2014,Yu, et al, 2014, the association between TREM2 variants and AD has been confirmed by most studies (Benitez, et al, 2013,Giraldo, et al, 2013,Gonzalez Murcia, et al, 2013,Luis, et al, 2014,Slattery, et al, 2014. Moreover, TREM2 variants were also found to be associated with frontotemporal dementia-like syndrome or FTD (Borroni, et al, 2014,R.…”

Section: Introductionmentioning

confidence: 90%

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Triggering receptor expressed on myeloid cells-2 is involved in prion-induced microglial activation but does not contribute to prion pathogenesis in mouse brains

Zhu

Herrmann

et al. 2015

Neurobiology of Aging

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Dysfunctional variants of the innate immune cell surface receptor TREM2 (triggering receptor expressed on myeloid cells-2) were identified as major genetic risk factors for Alzheimer's disease and other neurodegenerative conditions. Here we assessed a possible involvement of TREM2 in prion disease. We report that TREM2 expression by microglia is significantly up-regulated upon prion infection. However, depletion of TREM2 did not affect disease incubation time and survival after intracerebral prion infection. Interestingly, markers of microglial activation were attenuated in prion-infected TREM2(-/-) mice, suggesting an involvement of TREM2 in prion-induced microglial activation. Further phenotype profiling of microglia revealed that TREM2 deficiency did not change microglial phenotypes. We conclude that TREM2 is involved in prion-induced microglial activation but does not noticeably modulate the pathogenesis of experimental prion infections. | P a g e AbstractDysfunctional variants of the innate immune cell surface receptor TREM2 (triggering receptor expressed on myeloid cells-2) were identified as major genetic risk factors for Alzheimer's disease and other neurodegenerative conditions. Here we assessed a possible involvement of TREM2 in prion disease. We report that TREM2 expression by microglia is significantly upregulated upon prion infection. However, depletion of TREM2 did not affect disease incubation time and survival after intracerebral prion infection. Interestingly, markers of microglial activation were attenuated in prion-infected TREM2 -/-mice, suggesting an involvement of TREM2 in prion-induced microglial activation. Further phenotype profiling of microglia revealed that TREM2 deficiency did not change microglial phenotypes. We conclude that TREM2 is involved in prion-induced microglial activation, but does not noticeably modulate the pathogenesis of experimental prion infections.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 90%

Triggering receptor expressed on myeloid cells-2 is involved in prion-induced microglial activation but does not contribute to prion pathogenesis in mouse brains

Zhu

Herrmann

et al. 2015

Neurobiology of Aging

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“…Finally, 14 studies were included in the meta-analysis. 13 studies for rs75932628 [11,12,18,19,21,[27][28][29][30][31][32][33][34], 3 studies for rs104894002 [11,32,35], and 4 studies for rs143332484 [12,28,31,32,35]. The selected study characteristics and allele information are shown in Tables 1 and 2, respectively.…”

Section: Characteristics Of Included Studiesmentioning

confidence: 99%

“…Inconsistent results for associations between rs75932628, rs104894002 (predicted to cause a Q33X substitution), or rs143332484 (predicted to cause a R62H substitution) and AD risk have been constantly reported [11,19,21]. Therefore, we performed a meta-analysis to evaluate the association between the three variants and the risk of AD.…”

Section: Introductionmentioning

confidence: 99%

TREM2 variants and risk of Alzheimer’s disease: a meta-analysis

Liu

Wang

2015

Neurol Sci

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Recent studies show that heterozygous variant of triggering receptor expressed on myeloid cells 2 (TREM2) increase the risk of Alzheimer's disease (AD) but with inconclusive results. Here, we conducted a meta-analysis to summarize and clarify the association between TREM2 variants and AD, and examined the relationship between TREM2 genetic variant and the etiology of AD. Relevant case-control studies were retrieved and collected according to established inclusion criteria. Odds ratio (OR) and 95% confidence interval (95% CI) were used to estimate the associations between three TREM2 variants (rs75932628, rs104894002, and rs143332484) and AD. In overall meta-analysis, the summary ORs for rs75932628, rs104894002, and rs143332484 were 2.70 [95% CI: 2.24, 3.24; P < 0.001], 7.21 (95% CI: 1.28, 40.78; P = 0.025), and 1.65 (95% CI: 1.24, 2.21; P = 0.001), respectively, indicating that the TREM2 rs75932628, rs104894002, and rs143332484 may contribute to AD risk. However, sensitivity analysis showed that the results of rs104894002 and rs143332484 should be interpreted with caution, and larger sample size, particularly in different ethnicities, are needed to validate the two variants. The current meta-analysis demonstrates that TREM2 is a candidate gene for AD susceptibility, and TREM2 variant rs75932628 may be a risk factor for AD.

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“…Over the last year, a series of independent studies have reported a strong association of the triggering receptor expressed on myeloid cells 2 ( TREM2 ) gene with Alzheimer’s disease (AD) [1–7]. For one particular nonsynonymous variant, rs75932628 (encoding R47H), the association reached genome-wide significance [1,2].…”

Section: Introductionmentioning

confidence: 99%

The triggering receptor expressed on myeloid cells 2 (TREM2) is associated with enhanced inflammation, neuropathological lesions and increased risk for Alzheimer's dementia

Roussos

Katsel

Fam

et al. 2014

Alzheimer's & Dementia

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Objective To elucidate the relationship between the triggering receptor expressed on myeloid cells 2 (TREM2) risk variant, neuropathological lesions, alterations in gene and protein expression and severity of neuroinflammation. Methods Genetic association study of the R47H TREM2 variant with Alzheimer’s disease, neuropathology and changes in TREM2 and TYRO protein tyrosine kinase-binding protein (TYROBP) gene and protein expression and neuroinflammatory markers. Results The TREM2 variant is associated with: (i) Alzheimer’s disease (odds ratio: 4.76; P = 0.014); (ii) increased density of amyloid plaques and neurofibrillary tangles in multiple brain regions; (iii) increased TREM2 (P = 0.041) and TYROBP (P = 0.006) gene expression; (iv) decreased TREM2 protein levels (P = 0.016); and (v) upregulation of proinflammatory cytokines (RANTES and IFN-gamma) (P = 0.003) and nominal downregulation of protective markers (α2 macroglobulin, IL-4 and ApoA1) (P = 0.018). Conclusions These findings link the TREM2 missense mutation with specific molecular abnormalities and increases in neuropathological lesions in the human brain.

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Assessment of TREM2 rs75932628 association with Alzheimer's disease in a population-based sample: the Cache County Study

Cited by 48 publications

References 11 publications

Triggering receptor expressed on myeloid cells-2 is involved in prion-induced microglial activation but does not contribute to prion pathogenesis in mouse brains

Triggering receptor expressed on myeloid cells-2 is involved in prion-induced microglial activation but does not contribute to prion pathogenesis in mouse brains

TREM2 variants and risk of Alzheimer’s disease: a meta-analysis

The triggering receptor expressed on myeloid cells 2 (TREM2) is associated with enhanced inflammation, neuropathological lesions and increased risk for Alzheimer's dementia

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