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path(MESH:"Frontotemporal Dementia")

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Entity

Name
Frontotemporal Dementia
Namespace
mesh
Namespace Version
20180828
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/1b20f0637c395f8aa89c2e2e342d7b704062c242/external/mesh-names.belns

Appears in Networks 15

Promoting the clearance of neurotoxic proteins in neurodegenerative disorders of ageing v1.0.0

Interplay of pathogenic forms of human tau with different autophagic pathways v1.0.1

Tau clearance mechanisms and their possible role in the pathogenesis of Alzheimer disease v1.0.0

Extracellular Monomeric and Aggregated Tau Efficiently Enter Human Neurons through Overlapping but Distinct Pathways v1.0.1

TFEB enhances astroglial uptake of extracellular tau species and reduces tau spreading v1.0.0

Tau oligomers-Cytotoxicity, propagation, and mitochondrial damage v1.0.0

Tau oligomers-Cytotoxicity, propagation, and mitochondrial damage from Shafiei et al., 2017

Tau Protein Hyperphosphorylation and Aggregation in Alzheimer’s Disease and Other Tauopathies, and Possible Neuroprotective Strategies v1.0.0

Tau Biochemistry v1.2.5

Tau Biochemistry Section of NESTOR

TAU and Interaction Partners v1.2.5

TAU Interactions Section of NESTOR

Tau Modifications v1.9.5

Tau Modifications Sections of NESTOR

Axonal Transport, Tau Protein, and Neurodegeneration in Alzheimer’s Disease v1.0.0

PP2A and Alzheimer Disease v1.0.0

Alzheimer’s disease and the autophagic-lysosomal system v1.0.0

Tau in physiology and pathology v1.0.0

mTOR-Related Brain Dysfunctions in Neuropsychiatric Disorders v1.0.0

In-Edges 22

p(HGNC:C9orf72) association path(MESH:"Frontotemporal Dementia") View Subject | View Object

However, in light of common risk genes such as SQSTM1 (which encodes p62) and chromosome 9 open reading frame 72 (C9ORF72), FTD is increasingly linked to ALS 82,83 . PubMed:30116051

Appears in Networks:
Annotations
MeSH
Dopaminergic Neurons
MeSH
Frontotemporal Dementia

p(HGNC:SQSTM1) association path(MESH:"Frontotemporal Dementia") View Subject | View Object

However, in light of common risk genes such as SQSTM1 (which encodes p62) and chromosome 9 open reading frame 72 (C9ORF72), FTD is increasingly linked to ALS 82,83 . PubMed:30116051

Appears in Networks:
Annotations
MeSH
Dopaminergic Neurons
MeSH
Frontotemporal Dementia

p(HGNC:MAPT, var("p.P301L")) association path(MESH:"Frontotemporal Dementia") View Subject | View Object

PSA was identified as a potential player in tau pathology through a microarray analysis of gene expression in disease-vulnerable vs. disease-resistant brain regions in JNPL3 mice that overexpress a mutant form of tau (P301L) found in the disease frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). These mice develop neurodegeneration in the cortex while the cerebellum is relatively spared [although in the original description of these animals pathology was found in the deep cerebellar nuclei (27)]. PubMed:24027553

Appears in Networks:
Annotations
Text Location
Review

p(HGNC:NPEPPS) positiveCorrelation path(MESH:"Frontotemporal Dementia") View Subject | View Object

Interestingly, PSA was found to be elevated in the cerebellum of these TAUP301L mice (10). The levels of PSA are also higher in human cerebellum compared to cortex in both controls and FTD cases. A slight elevation in PSA was also observed in FTD cortices compared to controls. PubMed:24027553

Appears in Networks:
Annotations
MeSH
Cerebellum
Text Location
Review

p(HGNC:MAPT, var("p.Pro301Ser")) increases path(MESH:"Frontotemporal Dementia") View Subject | View Object

We used the tau P301S variant, an autosomal dominant mutation that causes early onset FTD with high penetrance (Bugiani et al., 1999; Guo et al., 2017) PubMed:29590627

Appears in Networks:

p(HGNC:MAPT) positiveCorrelation path(MESH:"Frontotemporal Dementia") View Subject | View Object

More recently, patients affected with FTD and AD, were found to have high levels of total tau and phosphorylated tau (p-T181 and p-S396; Saman et al., 2012) PubMed:28420982

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebrospinal Fluid
MeSH
Alzheimer Disease

p(HGNC:MAPT, pmod(Ph, Ser, 396)) positiveCorrelation path(MESH:"Frontotemporal Dementia") View Subject | View Object

More recently, patients affected with FTD and AD, were found to have high levels of total tau and phosphorylated tau (p-T181 and p-S396; Saman et al., 2012) PubMed:28420982

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebrospinal Fluid
MeSH
Alzheimer Disease

p(HGNC:MAPT, pmod(Ph, Thr, 181)) positiveCorrelation path(MESH:"Frontotemporal Dementia") View Subject | View Object

More recently, patients affected with FTD and AD, were found to have high levels of total tau and phosphorylated tau (p-T181 and p-S396; Saman et al., 2012) PubMed:28420982

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebrospinal Fluid
MeSH
Alzheimer Disease

p(HGNC:MAPT, var("p.Arg406Trp")) positiveCorrelation path(MESH:"Frontotemporal Dementia") View Subject | View Object

Poorkaj et al. reported two exonic mutations (P301L and V337M) in two families with FTDP-17 [139], while Hutton et al. reported six different mutations in 10 families: three of these mutations (G272V, P301L and R406W) were missense mutations in exons, while the other three were in the 5' splice site of exon 10 [140]. PubMed:26751493

Appears in Networks:

p(HGNC:MAPT, var("p.Gly272Val")) positiveCorrelation path(MESH:"Frontotemporal Dementia") View Subject | View Object

Poorkaj et al. reported two exonic mutations (P301L and V337M) in two families with FTDP-17 [139], while Hutton et al. reported six different mutations in 10 families: three of these mutations (G272V, P301L and R406W) were missense mutations in exons, while the other three were in the 5' splice site of exon 10 [140]. PubMed:26751493

Appears in Networks:

p(HGNC:MAPT, var("p.Pro301Leu")) positiveCorrelation path(MESH:"Frontotemporal Dementia") View Subject | View Object

Poorkaj et al. reported two exonic mutations (P301L and V337M) in two families with FTDP-17 [139], while Hutton et al. reported six different mutations in 10 families: three of these mutations (G272V, P301L and R406W) were missense mutations in exons, while the other three were in the 5' splice site of exon 10 [140]. PubMed:26751493

Appears in Networks:

p(HGNC:MAPT, var("p.Val337Met")) positiveCorrelation path(MESH:"Frontotemporal Dementia") View Subject | View Object

Poorkaj et al. reported two exonic mutations (P301L and V337M) in two families with FTDP-17 [139], while Hutton et al. reported six different mutations in 10 families: three of these mutations (G272V, P301L and R406W) were missense mutations in exons, while the other three were in the 5' splice site of exon 10 [140]. PubMed:26751493

Appears in Networks:

p(HGNC:PSEN1, var("p.Gly183Val")) positiveCorrelation path(MESH:"Frontotemporal Dementia") View Subject | View Object

A PSEN1 mutation causes a Pick’s disease phenotype including FTD tau pathology without deposition of Abeta [145]; some MAPT single nucleotide polymorphisms have also been linked to sporadic Parkinson’s disease (PD, [146]); PubMed:26751493

Appears in Networks:

p(HBP:"Tau isoform F (441 aa)", var("p.Pro301Leu")) increases path(MESH:"Frontotemporal Dementia") View Subject | View Object

We found that in the visual cortex, neurons containing conspicuous quantities of mislocalized and aggregated tau nonetheless appear to have a normal capacity to integrate dendritic inputs and respond robustly to visual stimuli and also maintain normal somatic baseline calcium levels. In particular, we show that individual NFT-bearing neurons can respond robustly after integrating sensory inputs and are functionally indistinguishable from neighboring non–NFT-bearing neurons. These results demonstrate that NFT-bearing neurons remain functionally integrated in cortical circuits. PubMed:24368848

Appears in Networks:
Annotations
MeSH
Frontotemporal Dementia

g(DBSNP:rs63750424) positiveCorrelation path(MESH:"Frontotemporal Dementia") View Subject | View Object

Mutations of a conserved arginine residue in the Nterminus of tau, found in patients with FTDP-17, affect its binding to dynactin, which is abnormally distributed in the retinal ganglion cell axons of transgenic mice expressing human tau with a mutation in the microtubule-binding domain. PubMed:8391280

Appears in Networks:
Annotations
Uberon
ganglionic layer of retina

p(HGNC:MAPT, var("p.Pro301Ser")) increases path(MESH:"Frontotemporal Dementia") View Subject | View Object

We developed a transgenic mouse, named TPR50, harboring human P301S tau. Tau phosphorylation in the hippocampus of TPR50 mice increased with age, particularly at S202/T205. Therefore, cognitive dysfunction in TPR50 mice may result from early MT dysfunction and impaired axonal transport rather than accumulation of insoluble tau and neurodegeneration. PubMed:24406748

Appears in Networks:

p(FPLX:PPP2) association path(MESH:"Frontotemporal Dementia") View Subject | View Object

So far, the most explored pathologies in which PP2A is implicated are cancer, and some viral and parasitic diseases [44]. More recently, PP2A has been investigated in FTLD linked to mutations in the tau gene [45]. PubMed:22299660

Appears in Networks:

p(HBP:"4R tau") positiveCorrelation path(MESH:"Frontotemporal Dementia") View Subject | View Object

Evidently, this argues for critical levels of protein tau-4R in the pathology of FTD and by exten- sion, in AD. PubMed:12428809

Appears in Networks:

p(HGNC:MAPT) association path(MESH:"Frontotemporal Dementia") View Subject | View Object

Dysregulation of tau proteins can produce a spectrum of neurodegenerative diseases or tauopathies characterized by dementia and tau deposition, including AD, frontotemporal dementia (FTD), Niemann- Pick disease, corticobasal degeneration (CBD), tangle-only dementia (TOD) and progressive supranuclear palsy (PSP). PubMed:29758300

Appears in Networks:

p(HGNC:TARDBP, pmod(HBP:misfolding)) positiveCorrelation path(MESH:"Frontotemporal Dementia") View Subject | View Object

Another common proteinopathy occurs from the misfolding of TARDNA binding protein 43 kDa (TDP-43), which is primarily seen in amyotrophic lateral sclerosis (ALS) and FTD [67] PubMed:29758300

Appears in Networks:

p(HGNC:MAPT, pmod(Ac, Lys, 280)) positiveCorrelation path(MESH:"Frontotemporal Dementia") View Subject | View Object

By contrast, acetylation of tau at Lys280 has been detected in AD and other tauopathies, including AGD, tangle-predominant senile dementia (TPSD), PiD, FTDP‑17 and PSP, and is pathological PubMed:26631930

Appears in Networks:

p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) positiveCorrelation path(MESH:"Frontotemporal Dementia") View Subject | View Object

Moreover, pathological deposition of hyperphosphorylated MAP-tau (MAPT), which is the hallmark of several neurodegenerative disorders such as AD and frontotemporal dementia (FTD), has been described in elderly subjects with schizophrenia PubMed:30061532

Appears in Networks:

Out-Edges 25

path(MESH:"Frontotemporal Dementia") association p(HGNC:SQSTM1) View Subject | View Object

However, in light of common risk genes such as SQSTM1 (which encodes p62) and chromosome 9 open reading frame 72 (C9ORF72), FTD is increasingly linked to ALS 82,83 . PubMed:30116051

Appears in Networks:
Annotations
MeSH
Dopaminergic Neurons
MeSH
Frontotemporal Dementia

path(MESH:"Frontotemporal Dementia") association p(HGNC:C9orf72) View Subject | View Object

However, in light of common risk genes such as SQSTM1 (which encodes p62) and chromosome 9 open reading frame 72 (C9ORF72), FTD is increasingly linked to ALS 82,83 . PubMed:30116051

Appears in Networks:
Annotations
MeSH
Dopaminergic Neurons
MeSH
Frontotemporal Dementia

path(MESH:"Frontotemporal Dementia") increases act(p(HGNC:ABL1)) View Subject | View Object

ABL1 is overactivated in AD and tauopathies such as FTD 152 . PubMed:30116051

Appears in Networks:
Annotations
MeSH
Dopaminergic Neurons
MeSH
Machado-Joseph Disease

path(MESH:"Frontotemporal Dementia") increases path(MESH:"Proteostasis Deficiencies") View Subject | View Object

It is well accepted that loss of proteostasis occurs gradually with age and underlies the basis of severe neurodegenerative disorders such as Parkinson’s disease, Huntington’s disease, Alzheimer’s disease, and other types of frontotemporal dementia (Prahlad & Morimoto, 2009; Voisine et al., 2010; Morimoto & Cuervo, 2014) PubMed:29024336

Appears in Networks:
Annotations
Confidence
High
MeSH
Brain
MeSH
Neurons

path(MESH:"Frontotemporal Dementia") association p(HGNC:MAPT, var("p.P301L")) View Subject | View Object

PSA was identified as a potential player in tau pathology through a microarray analysis of gene expression in disease-vulnerable vs. disease-resistant brain regions in JNPL3 mice that overexpress a mutant form of tau (P301L) found in the disease frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). These mice develop neurodegeneration in the cortex while the cerebellum is relatively spared [although in the original description of these animals pathology was found in the deep cerebellar nuclei (27)]. PubMed:24027553

Appears in Networks:
Annotations
Text Location
Review

path(MESH:"Frontotemporal Dementia") positiveCorrelation p(HGNC:NPEPPS) View Subject | View Object

Interestingly, PSA was found to be elevated in the cerebellum of these TAUP301L mice (10). The levels of PSA are also higher in human cerebellum compared to cortex in both controls and FTD cases. A slight elevation in PSA was also observed in FTD cortices compared to controls. PubMed:24027553

Appears in Networks:
Annotations
MeSH
Cerebellum
Text Location
Review

path(MESH:"Frontotemporal Dementia") increases r(HGNC:TFEB) View Subject | View Object

. In addition, human brains diagnosed with frontotemporal demen- tia (FTD) demonstrated an increase in transcriptional levels of TFEB and TFEB lysosomal target gene LAMP1 PubMed:30108137

Appears in Networks:

path(MESH:"Frontotemporal Dementia") increases r(HGNC:LAMP1) View Subject | View Object

. In addition, human brains diagnosed with frontotemporal demen- tia (FTD) demonstrated an increase in transcriptional levels of TFEB and TFEB lysosomal target gene LAMP1 PubMed:30108137

Appears in Networks:

path(MESH:"Frontotemporal Dementia") increases p(HGNC:TFEB) View Subject | View Object

On the protein level, TFEB lysosomal target genes LAMP1 and Cathep- sin D (CTSD) are also increased in the FTD frontal cortex relative to normal subjects, and TFEB protein levels trended increased with statistical significance in the CBD group PubMed:30108137

Appears in Networks:

path(MESH:"Frontotemporal Dementia") increases p(HGNC:CTSD) View Subject | View Object

On the protein level, TFEB lysosomal target genes LAMP1 and Cathep- sin D (CTSD) are also increased in the FTD frontal cortex relative to normal subjects, and TFEB protein levels trended increased with statistical significance in the CBD group PubMed:30108137

Appears in Networks:

path(MESH:"Frontotemporal Dementia") positiveCorrelation p(HGNC:MAPT) View Subject | View Object

More recently, patients affected with FTD and AD, were found to have high levels of total tau and phosphorylated tau (p-T181 and p-S396; Saman et al., 2012) PubMed:28420982

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebrospinal Fluid
MeSH
Alzheimer Disease

path(MESH:"Frontotemporal Dementia") positiveCorrelation p(HGNC:MAPT, pmod(Ph, Ser, 396)) View Subject | View Object

More recently, patients affected with FTD and AD, were found to have high levels of total tau and phosphorylated tau (p-T181 and p-S396; Saman et al., 2012) PubMed:28420982

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebrospinal Fluid
MeSH
Alzheimer Disease

path(MESH:"Frontotemporal Dementia") positiveCorrelation p(HGNC:MAPT, pmod(Ph, Thr, 181)) View Subject | View Object

More recently, patients affected with FTD and AD, were found to have high levels of total tau and phosphorylated tau (p-T181 and p-S396; Saman et al., 2012) PubMed:28420982

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebrospinal Fluid
MeSH
Alzheimer Disease

path(MESH:"Frontotemporal Dementia") positiveCorrelation p(HGNC:MAPT, var("p.Pro301Leu")) View Subject | View Object

Poorkaj et al. reported two exonic mutations (P301L and V337M) in two families with FTDP-17 [139], while Hutton et al. reported six different mutations in 10 families: three of these mutations (G272V, P301L and R406W) were missense mutations in exons, while the other three were in the 5' splice site of exon 10 [140]. PubMed:26751493

Appears in Networks:

path(MESH:"Frontotemporal Dementia") positiveCorrelation p(HGNC:MAPT, var("p.Val337Met")) View Subject | View Object

Poorkaj et al. reported two exonic mutations (P301L and V337M) in two families with FTDP-17 [139], while Hutton et al. reported six different mutations in 10 families: three of these mutations (G272V, P301L and R406W) were missense mutations in exons, while the other three were in the 5' splice site of exon 10 [140]. PubMed:26751493

Appears in Networks:

path(MESH:"Frontotemporal Dementia") positiveCorrelation p(HGNC:MAPT, var("p.Gly272Val")) View Subject | View Object

Poorkaj et al. reported two exonic mutations (P301L and V337M) in two families with FTDP-17 [139], while Hutton et al. reported six different mutations in 10 families: three of these mutations (G272V, P301L and R406W) were missense mutations in exons, while the other three were in the 5' splice site of exon 10 [140]. PubMed:26751493

Appears in Networks:

path(MESH:"Frontotemporal Dementia") positiveCorrelation p(HGNC:MAPT, var("p.Arg406Trp")) View Subject | View Object

Poorkaj et al. reported two exonic mutations (P301L and V337M) in two families with FTDP-17 [139], while Hutton et al. reported six different mutations in 10 families: three of these mutations (G272V, P301L and R406W) were missense mutations in exons, while the other three were in the 5' splice site of exon 10 [140]. PubMed:26751493

Appears in Networks:

path(MESH:"Frontotemporal Dementia") positiveCorrelation p(HGNC:PSEN1, var("p.Gly183Val")) View Subject | View Object

A PSEN1 mutation causes a Pick’s disease phenotype including FTD tau pathology without deposition of Abeta [145]; some MAPT single nucleotide polymorphisms have also been linked to sporadic Parkinson’s disease (PD, [146]); PubMed:26751493

Appears in Networks:

path(MESH:"Frontotemporal Dementia") positiveCorrelation g(DBSNP:rs63750424) View Subject | View Object

Mutations of a conserved arginine residue in the Nterminus of tau, found in patients with FTDP-17, affect its binding to dynactin, which is abnormally distributed in the retinal ganglion cell axons of transgenic mice expressing human tau with a mutation in the microtubule-binding domain. PubMed:8391280

Appears in Networks:
Annotations
Uberon
ganglionic layer of retina

path(MESH:"Frontotemporal Dementia") positiveCorrelation p(HBP:"4R tau") View Subject | View Object

Evidently, this argues for critical levels of protein tau-4R in the pathology of FTD and by exten- sion, in AD. PubMed:12428809

Appears in Networks:

path(MESH:"Frontotemporal Dementia") association p(FPLX:PPP2) View Subject | View Object

So far, the most explored pathologies in which PP2A is implicated are cancer, and some viral and parasitic diseases [44]. More recently, PP2A has been investigated in FTLD linked to mutations in the tau gene [45]. PubMed:22299660

Appears in Networks:

path(MESH:"Frontotemporal Dementia") association p(HGNC:MAPT) View Subject | View Object

Dysregulation of tau proteins can produce a spectrum of neurodegenerative diseases or tauopathies characterized by dementia and tau deposition, including AD, frontotemporal dementia (FTD), Niemann- Pick disease, corticobasal degeneration (CBD), tangle-only dementia (TOD) and progressive supranuclear palsy (PSP). PubMed:29758300

Appears in Networks:

path(MESH:"Frontotemporal Dementia") positiveCorrelation p(HGNC:TARDBP, pmod(HBP:misfolding)) View Subject | View Object

Another common proteinopathy occurs from the misfolding of TARDNA binding protein 43 kDa (TDP-43), which is primarily seen in amyotrophic lateral sclerosis (ALS) and FTD [67] PubMed:29758300

Appears in Networks:

path(MESH:"Frontotemporal Dementia") positiveCorrelation p(HGNC:MAPT, pmod(Ac, Lys, 280)) View Subject | View Object

By contrast, acetylation of tau at Lys280 has been detected in AD and other tauopathies, including AGD, tangle-predominant senile dementia (TPSD), PiD, FTDP‑17 and PSP, and is pathological PubMed:26631930

Appears in Networks:

path(MESH:"Frontotemporal Dementia") positiveCorrelation p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) View Subject | View Object

Moreover, pathological deposition of hyperphosphorylated MAP-tau (MAPT), which is the hallmark of several neurodegenerative disorders such as AD and frontotemporal dementia (FTD), has been described in elderly subjects with schizophrenia PubMed:30061532

Appears in Networks:

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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.