|
Frontotemporal dementia
|
0.200 |
GeneticVariation
|
disease |
BEFREE |
Age at symptom onset in genetic FTD is variable with recently identified genetic modifiers including TMEM106B (in GRN carriers particularly) and a polymorphism at a locus containing two overlapping genes LOC101929163 and C6orf10 (in C9orf72 carriers).
|
31119452 |
2019 |
|
Frontotemporal dementia
|
0.200 |
GeneticVariation
|
disease |
BEFREE |
The TMEM106B rs1990622<sup>T</sup> allele, linked to increased risk of FTD, associated with greater MMSE decline over time in PD subjects but not in AD or MCI subjects.
|
30973966 |
2019 |
|
Frontotemporal dementia
|
0.200 |
Biomarker
|
disease |
BEFREE |
Loss of Tmem106b is unable to ameliorate frontotemporal dementia-like phenotypes in an AAV mouse model of C9ORF72-repeat induced toxicity.
|
29855382 |
2018 |
|
Frontotemporal dementia
|
0.200 |
Biomarker
|
disease |
BEFREE |
As TMEM106B is a risk factor for frontotemporal dementia caused by both C9orf72 and progranulin mutations, and antisense oligonucleotides are showing promise as therapeutics for neurodegenerative diseases, our data suggests a potential new strategy for treating the wide range of frontotemporal dementias associated with endolysosomal dysfunction.
|
30496365 |
2018 |
|
Frontotemporal dementia
|
0.200 |
GeneticVariation
|
disease |
BEFREE |
Multiple genome-wide association studies have shown that risk of FTD in GRN mutation carriers is modified by polymorphisms in TMEM106B, which encodes a lysosomal membrane protein.
|
29929528 |
2018 |
|
Frontotemporal dementia
|
0.200 |
GeneticVariation
|
disease |
BEFREE |
Polymorphisms in TMEM106B are thought to modify disease onset in frontotemporal dementia, but its relation to myelination is not understood.
|
29186371 |
2017 |
|
Frontotemporal dementia
|
0.200 |
GeneticVariation
|
disease |
BEFREE |
We subsequently performed a genome-wide association study and identified the TMEM106B and GRN gene loci, previously associated with frontotemporal dementia, as determinants of Δ-aging in the cerebral cortex with genome-wide significance.
|
28330615 |
2017 |
|
Frontotemporal dementia
|
0.200 |
GeneticVariation
|
disease |
BEFREE |
Recent studies found that two polymorphisms (rs363371 and rs363324) in VMAT2 might be a risk factor for Parkinson's disease (PD) in Caucasians, while the two other variants (rs1990622 and rs3173615) in TMEM106B increased the risk for frontotemporal dementia (FTD).
|
28477711 |
2017 |
|
Frontotemporal dementia
|
0.200 |
GeneticVariation
|
disease |
BEFREE |
TMEM106B polymorphism, rs1990622 T/C) on grey matter volume in a large cohort of presymptomatic subjects bearing frontotemporal dementia-related pathogenic mutations.
|
28460069 |
2017 |
|
Frontotemporal dementia
|
0.200 |
GeneticVariation
|
disease |
BEFREE |
TMEM106B and ApoE polymorphisms in CHMP2B-mediated frontotemporal dementia (FTD-3).
|
28888721 |
2017 |
|
Frontotemporal dementia
|
0.200 |
Biomarker
|
disease |
BEFREE |
Loss of TMEM106B Ameliorates Lysosomal and Frontotemporal Dementia-Related Phenotypes in Progranulin-Deficient Mice.
|
28728022 |
2017 |
|
Frontotemporal dementia
|
0.200 |
GeneticVariation
|
disease |
BEFREE |
In addition, the finding in the stage 1 sample that AD risk is significantly influenced by the interaction of APOE with rs1595014 in TMEM106B (P=1·6 × 10(-7)) is noteworthy, because TMEM106B variants have previously been associated with risk of frontotemporal dementia.
|
25778476 |
2016 |
|
Frontotemporal dementia
|
0.200 |
AlteredExpression
|
disease |
BEFREE |
These findings suggest that the up-regulation of TMEM106B may increase the risk of FTLD by directly causing neurotoxicity and a pathological phenotype linked to FTLD-TDP.
|
27563066 |
2016 |
|
Frontotemporal dementia
|
0.200 |
AlteredExpression
|
disease |
BEFREE |
Increased expression of the frontotemporal dementia risk factor TMEM106B causes C9orf72-dependent alterations in lysosomes.
|
27126638 |
2016 |
|
Frontotemporal dementia
|
0.200 |
GeneticVariation
|
disease |
BEFREE |
In this manuscript, we review the initial discovery and replication studies describing TMEM106B variants as disease risk factors and modifiers in TDP-43 proteinopathies, such as FTLD-TDP caused by progranulin (GRN) or chromosome 9 open reading frame 72 (C9orf72) mutations, as well as Alzheimer's disease and hippocampal sclerosis.
|
27543298 |
2016 |
|
Frontotemporal dementia
|
0.200 |
Biomarker
|
disease |
BEFREE |
Recent evidence suggests that two other genes associated with FTD, GRN and TMEM106B are important for lysosomal function.
|
26358247 |
2015 |
|
Frontotemporal dementia
|
0.200 |
GeneticVariation
|
disease |
BEFREE |
Association of TMEM106B rs1990622 marker and frontotemporal dementia: evidence for a recessive effect and meta-analysis.
|
25096617 |
2015 |
|
Frontotemporal dementia
|
0.200 |
GeneticVariation
|
disease |
BEFREE |
It has been demonstrated that the TMEM106B polymorphism is associated with GRN-related frontotemporal dementia and affects age at onset in GRN mutation carriers.
|
24343233 |
2014 |
|
Frontotemporal dementia
|
0.200 |
GeneticVariation
|
disease |
BEFREE |
Further studies are needed to determine whether TMEM106B polymorphisms are associated with other genetic causes for FTD, including C9orf72 repeat expansions.
|
25085782 |
2014 |
|
Frontotemporal dementia
|
0.200 |
GeneticVariation
|
disease |
BEFREE |
Previous reports have shown that TMEM106B is a genetic modifier of FTLD-TDP caused by progranulin (GRN) mutations, with the major (risk) allele of rs1990622 associating with earlier age at onset of disease.
|
24442578 |
2014 |
|
Frontotemporal dementia
|
0.200 |
GeneticVariation
|
disease |
BEFREE |
Variants in transmembrane protein 106 B (TMEM106B) modify the disease penetrance of frontotemporal dementia (FTD) in carriers of progranulin (GRN) mutations.
|
24385136 |
2014 |
|
Frontotemporal dementia
|
0.200 |
AlteredExpression
|
disease |
BEFREE |
Finally, we show that TMEM106B neuronal expression is significantly more disorganized in FTLD-TDP cases with GRN mutations, compared to normal and disease controls, including FTLD-TDP cases without GRN mutations.
|
24252750 |
2013 |
|
Frontotemporal dementia
|
0.200 |
GeneticVariation
|
disease |
BEFREE |
TMEM106B p.T185S regulates TMEM106B protein levels: implications for frontotemporal dementia.
|
23742080 |
2013 |
|
Frontotemporal dementia
|
0.200 |
GeneticVariation
|
disease |
BEFREE |
The most significant association of TMEM106B single nucleotide polymorphisms with risk of FTLD-TDP was observed in patients with progranulin (GRN) mutations.
|
22511793 |
2012 |
|
Frontotemporal dementia
|
0.200 |
Biomarker
|
disease |
BEFREE |
TMEM106B, the risk gene for frontotemporal dementia, is regulated by the microRNA-132/212 cluster and affects progranulin pathways.
|
22895706 |
2012 |