Frontotemporal dementia
|
0.900 |
GeneticVariation
|
disease |
BEFREE |
In this international, retrospective cohort study, we collected data on age at symptom onset, age at death, and disease duration for patients with pathogenic mutations in the GRN and MAPT genes and pathological expansions in the C9orf72 gene through the Frontotemporal Dementia Prevention Initiative and from published papers.
|
31810826 |
2020 |
Frontotemporal dementia
|
0.900 |
GeneticVariation
|
disease |
BEFREE |
Importantly, this effect on GCase activity was rescued by treatment with saposin C. Together, these findings suggested that reduced GCase activity due to impaired processing of prosaposin may contribute to pathogenesis of FTD resulting from PGRN mutations.
|
31600775 |
2020 |
Frontotemporal dementia
|
0.900 |
Biomarker
|
disease |
BEFREE |
GRN null mutations are among the main genetic causes of frontotemporal dementia through progranulin haploinsufficiency.
|
31262553 |
2020 |
Frontotemporal dementia
|
0.900 |
GeneticVariation
|
disease |
BEFREE |
We identified 9 potentially pathogenic mutations in the AD-causal genes APP, PSEN1, PSEN2, and 6 mutations in a group of non-AD dementia-causal genes including the FTD-causal gene GRN and the VaD-causal gene NOTCH3.
|
30954774 |
2019 |
Frontotemporal dementia
|
0.900 |
Biomarker
|
disease |
BEFREE |
We identified and validated five novel CSF biomarkers in <i>GRN-</i>associated FTD.
|
31019994 |
2019 |
Frontotemporal dementia
|
0.900 |
Biomarker
|
disease |
BEFREE |
Our findings indicate that murine progranulin deficiency causes age-dependent neurophysiological and behavioral abnormalities thereby indicating their validity in modeling aspects of human frontotemporal dementia.
|
31639062 |
2019 |
Frontotemporal dementia
|
0.900 |
Biomarker
|
disease |
BEFREE |
Among the seven GRNs, GRN-3 is well characterized and is implicated within the context of FTD.
|
30782973 |
2019 |
Frontotemporal dementia
|
0.900 |
Biomarker
|
disease |
BEFREE |
This cell model can be valuable for the study of the role of PGRN in the pathogenesis in FTLD-TDP.
|
31626287 |
2019 |
Frontotemporal dementia
|
0.900 |
GeneticVariation
|
disease |
BEFREE |
Eligible participants (aged ≥18 years) either had frontotemporal dementia due to a pathogenic mutation in GRN, C9orf72, or MAPT (symptomatic mutation carriers) or were healthy at-risk first-degree relatives (either presymptomatic mutation carriers or non-carriers), and had at least two serum samples with a time interval of 6 months or more.
|
31701893 |
2019 |
Frontotemporal dementia
|
0.900 |
GeneticVariation
|
disease |
BEFREE |
We performed <sup>18</sup>F-flortaucipir imaging in patients with the FTD syndromes (n = 45): nonfluent variant primary progressive aphasia (nfvPPA) (n = 11), corticobasal syndrome (CBS) (n = 10), behavioral variant frontotemporal dementia (bvFTD) (n = 10), semantic variant primary progressive aphasia (svPPA) (n = 2) and FTD associated pathogenic genetic mutations microtubule-associated protein tau (MAPT) (n = 6), chromosome 9 open reading frame 72 (C9ORF72) (n = 5), and progranulin (GRN) (n = 1).
|
30704514 |
2019 |
Frontotemporal dementia
|
0.900 |
GeneticVariation
|
disease |
BEFREE |
The generation of in vivo models of FTD involves either targeting genes with known disease-causative mutations such as GRN and C9orf72 or genes encoding proteins that form the inclusions that characterize the disease pathologically, such as TDP-43 and FUS.
|
30582188 |
2019 |
Frontotemporal dementia
|
0.900 |
Biomarker
|
disease |
BEFREE |
In this study, we used mouse models to investigate the role of neuronal and microglial progranulin insufficiency in the development of FTD-like pathology and behavioral deficits.
|
30448285 |
2019 |
Frontotemporal dementia
|
0.900 |
GeneticVariation
|
disease |
BEFREE |
These disorders include progranulin (PGRN)-deficient forms of frontotemporal dementia caused by mutations in the <i>GRN</i> gene that lead to haploinsufficiency.
|
31330099 |
2019 |
Frontotemporal dementia
|
0.900 |
Biomarker
|
disease |
BEFREE |
Progranulin (PGRN) is best known as a glial protein for which deficiency leads to the most common inherited form of frontotemporal dementia.
|
31237618 |
2019 |
Frontotemporal dementia
|
0.900 |
GeneticVariation
|
disease |
BEFREE |
Through the study of 1131 unrelated Caucasian patients, we estimated that C9orf72 repeat expansions and GRN loss-of-function mutations account for 25.5% and 13.9% of FTLD-TDP patients, respectively.
|
30739198 |
2019 |
Frontotemporal dementia
|
0.900 |
AlteredExpression
|
disease |
BEFREE |
These findings suggest that the profile of TDP-43 inclusions, neuronal number, and microgliosis in the CA1 sector of FTLD-TDP type A cases may be influenced by GRN gene expression status.
|
31361008 |
2019 |
Frontotemporal dementia
|
0.900 |
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
|
0.900 |
Biomarker
|
disease |
BEFREE |
AAV-mediated progranulin gene (GRN) delivery has been proposed as a treatment for GRN-deficient frontotemporal dementia and neuronal ceroid lipofuscinosis, and recent studies using intraparenchymal AAV-Grn delivery to brain have shown moderate success in histopathologic and behavioral rescue in mouse models.
|
30559071 |
2019 |
Frontotemporal dementia
|
0.900 |
Biomarker
|
disease |
BEFREE |
Both inferences suggest a potential use of peripheral GRN mRNA or serum PGRN levels as biomarkers for families with FTD.
|
30475763 |
2019 |
Frontotemporal dementia
|
0.900 |
GeneticVariation
|
disease |
BEFREE |
Mutations in the progranulin (GRN) gene are a major cause of familial frontotemporal dementia.
|
30630176 |
2019 |
Frontotemporal dementia
|
0.900 |
GeneticVariation
|
disease |
BEFREE |
Presence on T2-weighted images of white matter hyperintensities (WMH) has been previously shown to be more commonly associated with GRN mutations rather than other forms of FTD.
|
31835286 |
2019 |
Frontotemporal dementia
|
0.900 |
GeneticVariation
|
disease |
BEFREE |
Of the cohort of 73 participants, eight mutation carriers (three GRN, five MAPT) developed clinical features of frontotemporal dementia ('converters').
|
30508042 |
2019 |
Frontotemporal dementia
|
0.900 |
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
|
0.900 |
Biomarker
|
disease |
BEFREE |
Here, we address these issues using an AAV vector (AAV-<i>Grn</i>) to deliver progranulin in <i>Grn</i><sup>-/-</sup> mice (both male and female), which model aspects of NCL and FTD pathology, developing lysosomal dysfunction, lipofuscinosis, and microgliosis.
|
29378861 |
2018 |
Frontotemporal dementia
|
0.900 |
Biomarker
|
disease |
BEFREE |
In the case of frontotemporal dementia (FTD), the ability to measure PGRN/GP88/GEP levels in plasma and cerebrospinal fluid may be useful in distinguishing PGRN mutation carriers among FTD populations at large.
|
29956271 |
2018 |