|
Alzheimer's Disease
|
|
0.900 |
GeneticVariation
|
BEFREE |
Recent studies have found an association between a variant in triggering receptor expressed on myeloid cells 2 (TREM2) (rs75932628-T) and both Alzheimer's disease (AD) and cognitive function in individuals aged 80-100 years.
|
24378087 |
2014 |
|
Alzheimer's Disease
|
|
0.900 |
GeneticVariation
|
BEFREE |
Recently, 3 rare coding variants significantly associated with Alzheimer's disease (AD) risk have been identified in western populations using whole exome sequencing method, including p.R47H in TREM2, p.V232M in PLD3, and p.T835M in UNC5C.
|
24866402 |
2014 |
|
Alzheimer's Disease
|
|
0.900 |
GeneticVariation
|
BEFREE |
Furthermore, carriers of the rs75932628 risk allele showed significantly increased levels of CSF-total-tau (P = .0110) but not Aβ42 suggesting that TREM2's role in AD may involve tau dysfunction.
|
25936935 |
2015 |
|
Alzheimer's Disease
|
|
0.900 |
GeneticVariation
|
BEFREE |
Recently, a rare missense variant (p.R47H) in the microglial activating gene TREM2 was found to increase the risk of several neurodegenerative diseases, including Alzheimer disease.
|
24535663 |
2014 |
|
Alzheimer's Disease
|
|
0.900 |
GeneticVariation
|
BEFREE |
Several studies have shown that TREM2 gene variant rs75932628-T increased the risks for Alzheimer's disease (AD), Parkinson's disease, frontotemporal dementia and amyotrophic lateral sclerosis.
|
25186950 |
2015 |
|
Alzheimer's Disease
|
|
0.900 |
GeneticVariation
|
BEFREE |
Although rs75932628 in triggering receptor expressed on myeloid cells 2 (TREM2) was shown to increase the risk for Alzheimer's disease, there is no agreement on the association between this variant and the risk for Parkinson's disease (PD).
|
26058955 |
2015 |
|
Alzheimer's Disease
|
|
0.900 |
GeneticVariation
|
BEFREE |
Three variants in TREM2 (rs75932628 (R47H), rs2234255 (H157Y), and rs143332484 (R62H)) were significantly associated with AD risk, but the similar associations between rs104894002 (Q33X), rs2234253 (T96K), rs142232675 (D87N), rs2234256 (L211P), and AD were not proven.
|
30883352 |
2019 |
|
Alzheimer's Disease
|
|
0.900 |
GeneticVariation
|
BEFREE |
Shedding is not altered for the R47H-mutated TREM2 protein that confers an increased risk for the development of Alzheimers disease.
|
28923481 |
2017 |
|
Alzheimer's Disease
|
|
0.900 |
GeneticVariation
|
BEFREE |
We did not identify the polymorphism p.R47H (rs75932628), strongly associated with an increased risk of developing Alzheimer's disease.
|
23759145 |
2013 |
|
Alzheimer's Disease
|
|
0.900 |
GeneticVariation
|
BEFREE |
These data suggest that the AD-associated TREM2 R47H variant increases risk for AD by conferring a loss of TREM2 function and enhancing neuritic dystrophy around plaques.
|
29859094 |
2018 |
|
Alzheimer's Disease
|
|
0.900 |
GeneticVariation
|
BEFREE |
Meta-analysis including 11 previously screened AD cohorts confirmed the association of p.R47H with AD (p = 2.93×10(-17)).
|
24119542 |
2014 |
|
Alzheimer's Disease
|
|
0.900 |
GeneticVariation
|
BEFREE |
Meta-analysis of rs75932628 genotypes imputed from genomewide association studies confirmed this association (P=0.002), as did direct genotyping of an additional series of 1887 patients with Alzheimer's disease and 4061 controls (P<0.001).
|
23150934 |
2013 |
|
Alzheimer's Disease
|
|
0.900 |
GeneticVariation
|
BEFREE |
In contrast, CSF sTREM2 levels were significantly higher in R47H carriers compared to non-carriers (P = 6×10(-3)), suggesting that this variant does not impact protein expression and increases AD risk through a different pathogenic mechanism than NHD variants.
|
26754641 |
2016 |
|
Alzheimer's Disease
|
|
0.900 |
GeneticVariation
|
BEFREE |
The rare variant R47H TREM2 is associated with an increased risk for Alzheimer's disease, supporting the hypothesis that TREM2 loss of function may exacerbate disease progression.
|
29599291 |
2018 |
|
Alzheimer's Disease
|
|
0.900 |
GeneticVariation
|
BEFREE |
While our results serve to confirm the association between R47H and risk of AD, the observed effect on risk was substantially smaller than that previously reported.
|
25186855 |
2014 |
|
Alzheimer's Disease
|
|
0.900 |
GeneticVariation
|
BEFREE |
In addition to Alzheimer's disease risk, we also examined the association of R47H with Alzheimer's disease-related phenotypes, including age-at-onset, psychosis, and amyloid deposition but found no significant association.
|
26058841 |
2015 |
|
Alzheimer's Disease
|
|
0.900 |
GeneticVariation
|
BEFREE |
We find p.R47H is a risk factor for AD, but not frontotemporal dementia or prion disease.
|
25160042 |
2014 |
|
Alzheimer's Disease
|
|
0.900 |
GeneticVariation
|
BEFREE |
The frequency of rs75932628-T as well as the amount of rare variants were higher in the AD patients than in the controls, but this did not reach a statistically significant association with AD (odds ratio: 4.8; 95% confidence interval: 0.54 to 43.6; p = 0.270).
|
26021840 |
2015 |
|
Alzheimer's Disease
|
|
0.900 |
GeneticVariation
|
BEFREE |
Lymphoblast-derived integration-free iPS cell line from a female 67-year-old Alzheimer's disease patient with TREM2 (R47H) missense mutation.
|
27789408 |
2016 |
|
Alzheimer's Disease
|
|
0.900 |
GeneticVariation
|
BEFREE |
Recent studies have identified a rare coding variant (p.R47H) in TREM2 that confers a high risk for Alzheimer's disease (AD).
|
24439484 |
2014 |
|
Alzheimer's Disease
|
|
0.900 |
GeneticVariation
|
GWASCAT |
A rare missense mutation (rs75932628-T) in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2), which was predicted to result in an R47H substitution, was found to confer a significant risk of Alzheimer's disease in Iceland (odds ratio, 2.92; 95% confidence interval [CI], 2.09 to 4.09; P=3.42×10(-10)).
|
23150908 |
2013 |
|
Alzheimer's Disease
|
|
0.900 |
GeneticVariation
|
BEFREE |
A meta-analysis comprising 32,598 subjects from 4 previous studies demonstrated the large effect of the p.R47H variant in AD risk (OR = 4.11, 95% CI = 2.99-5.68, p = 5.27×10(-18)).
|
24041969 |
2014 |
|
Alzheimer's Disease
|
|
0.900 |
GeneticVariation
|
BEFREE |
We generated transgenic mice expressing human CV or R47H TREM2 and lacking endogenous TREM2 in the 5XFAD AD model.
|
29321225 |
2018 |
|
Alzheimer's Disease
|
|
0.900 |
GeneticVariation
|
BEFREE |
Two rare variants have been nominally associated with AD risk or protection (TREM2 p.R47H, MAF approximately 0.002, OR approximately 4 and APP p.A673T, MAF approximately 0.0005, OR approximately 0.2).
|
28002825 |
2016 |
|
Alzheimer's Disease
|
|
0.900 |
GeneticVariation
|
BEFREE |
Given the reported antiinflammatory role of TREM2 in the brain, the R47H substitution may lead to an increased predisposition to Alzheimer's disease through impaired containment of inflammatory processes.
|
23150908 |
2013 |