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  3. PubMed:27574109

PubMed: 27574109

Title
Analysis of isoform-specific tau aggregates suggests a common toxic mechanism involving similar pathological conformations and axonal transport inhibition.
Journal
Neurobiology of aging
Volume
47
Issue
None
Pages
113-126
Date
2016-11-01
Authors
Abdelmesih B | Brady ST | Combs B | Cox K | Kanaan NM | Morfini G

Evidence e4df0e4a64
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In CBD, the characteristic astrocytic pathology (e.g. astrocytic plaques) showed extensive co-localization between TNT1, TOC1 and R1 in the frontal cortex (Fig. 5I–L).

a(HBP:"Corticobasal Degeneration") association a(HBP:"Tau oligomers") View Subject | View Object

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Frontal Lobe

a(HBP:"Corticobasal Degeneration") association a(HBP:"phosphatase-activating domain") View Subject | View Object

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Frontal Lobe

a(HBP:"Corticobasal Degeneration") association p(HGNC:MAPT) View Subject | View Object

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Frontal Lobe

a(HBP:"Tau oligomers") association a(HBP:"Corticobasal Degeneration") View Subject | View Object

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Frontal Lobe

a(HBP:"phosphatase-activating domain") association a(HBP:"Corticobasal Degeneration") View Subject | View Object

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MeSH
Frontal Lobe

p(HGNC:MAPT) association a(HBP:"Corticobasal Degeneration") View Subject | View Object

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Frontal Lobe

Evidence c27311f094
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Similarly, the characteristic Pick bodies in the frontal cortex were well labeled by TNT1, TOC1 and R1 in PiD tissue (Fig. 5M–P)

a(GO:"Pick body") association a(HBP:"Tau oligomers") View Subject | View Object

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Frontal Lobe
MeSH
Pick Disease of the Brain

a(GO:"Pick body") association a(HBP:"phosphatase-activating domain") View Subject | View Object

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Frontal Lobe
MeSH
Pick Disease of the Brain

a(GO:"Pick body") association p(HGNC:MAPT) View Subject | View Object

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Frontal Lobe
MeSH
Pick Disease of the Brain

a(HBP:"Tau oligomers") association a(GO:"Pick body") View Subject | View Object

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Frontal Lobe
MeSH
Pick Disease of the Brain

a(HBP:"phosphatase-activating domain") association a(GO:"Pick body") View Subject | View Object

Appears in Networks:
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MeSH
Frontal Lobe
MeSH
Pick Disease of the Brain

p(HGNC:MAPT) association a(GO:"Pick body") View Subject | View Object

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MeSH
Frontal Lobe
MeSH
Pick Disease of the Brain

Evidence 5df7f6fa52
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Right angle laser light scattering showed significantly greater scattered light intensity in all 4R tau isoforms when compared to 3R isoforms (one-way ANOVA with Holm-Sidak post-hoc, F(5, 18) = 60.22, p < 0.0001; Fig. 2A)

a(HBP:"3R tau") positiveCorrelation path(MESH:"Protein Aggregation, Pathological") View Subject | View Object

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a(HBP:"4R tau") positiveCorrelation path(MESH:"Protein Aggregation, Pathological") View Subject | View Object

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path(MESH:"Protein Aggregation, Pathological") positiveCorrelation a(HBP:"3R tau") View Subject | View Object

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path(MESH:"Protein Aggregation, Pathological") positiveCorrelation a(HBP:"4R tau") View Subject | View Object

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Evidence 46f3c729f0
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Similar results were seen in the ThS assay, where the 4R isoforms were significantly higher than 3R isoforms (one-way ANOVA with Holm-Sidak post-hoc, F(5, 18) = 19.99, p < 0.0001; Fig. 2B), and no differences were found in comparisons between the individual 4R isoforms or between the 3R isoforms

a(HBP:"3R tau") positiveCorrelation path(MESH:"Protein Aggregation, Pathological") View Subject | View Object

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a(HBP:"4R tau") positiveCorrelation path(MESH:"Protein Aggregation, Pathological") View Subject | View Object

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path(MESH:"Protein Aggregation, Pathological") positiveCorrelation a(HBP:"3R tau") View Subject | View Object

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path(MESH:"Protein Aggregation, Pathological") positiveCorrelation a(HBP:"4R tau") View Subject | View Object

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Evidence d35d04ff16
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In contrast, 3R isoforms were primarily composed of globular oligomers and only very rare long filaments were found (Fig. 2F–H)

a(HBP:"3R tau") positiveCorrelation bp(GO:"positive regulation of protein oligomerization") View Subject | View Object

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bp(GO:"positive regulation of protein oligomerization") positiveCorrelation a(HBP:"3R tau") View Subject | View Object

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Evidence 9d32d2a33d
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The band patterns in the immunoblots showed that the AD cases contained a mixture of isoforms, the PiD cases clearly contained 3R isoforms but also some 4R isoforms, while the vast majority of pathology in CBD cases were comprised of 4R tau isoforms

a(HBP:"3R tau") positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

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a(HBP:"3R tau") positiveCorrelation path(MESH:"Pick Disease of the Brain") View Subject | View Object

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a(HBP:"4R tau") positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

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a(HBP:"4R tau") positiveCorrelation path(MESH:"Pick Disease of the Brain") View Subject | View Object

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a(HBP:"4R tau") positiveCorrelation a(HBP:"Corticobasal Degeneration") View Subject | View Object

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a(HBP:"Corticobasal Degeneration") positiveCorrelation a(HBP:"4R tau") View Subject | View Object

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path(MESH:"Alzheimer Disease") positiveCorrelation a(HBP:"3R tau") View Subject | View Object

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path(MESH:"Alzheimer Disease") positiveCorrelation a(HBP:"4R tau") View Subject | View Object

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path(MESH:"Pick Disease of the Brain") positiveCorrelation a(HBP:"3R tau") View Subject | View Object

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path(MESH:"Pick Disease of the Brain") positiveCorrelation a(HBP:"4R tau") View Subject | View Object

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Evidence eed85f1c39
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A mixture of long, intermediate and short filaments, as well as globular oligomers were present in 4R isoform reactions (Fig. 2C–E)

a(HBP:"4R tau") positiveCorrelation bp(GO:"positive regulation of protein oligomerization") View Subject | View Object

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bp(GO:"positive regulation of protein oligomerization") positiveCorrelation a(HBP:"4R tau") View Subject | View Object

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Evidence 9f68af0d94
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Indeed, early pre-tangle neurons within the hippocampus were labeled with all antibodies in Braak I-II cases (Fig. 5A–D)

a(HBP:"Braak_Stage II") association a(HBP:"Tau oligomers") View Subject | View Object

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Hippocampus

a(HBP:"Braak_Stage II") association a(HBP:"phosphatase-activating domain") View Subject | View Object

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Hippocampus

a(HBP:"Braak_Stage I") association a(HBP:"Tau oligomers") View Subject | View Object

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Hippocampus

a(HBP:"Braak_Stage I") association a(HBP:"phosphatase-activating domain") View Subject | View Object

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MeSH
Hippocampus

a(HBP:"Braak_Stage I") association p(HGNC:MAPT) View Subject | View Object

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MeSH
Hippocampus

a(HBP:"Braak_Stage II") association p(HGNC:MAPT) View Subject | View Object

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MeSH
Hippocampus

a(HBP:"Tau oligomers") association a(HBP:pretangles) View Subject | View Object

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MeSH
Hippocampus

a(HBP:"Tau oligomers") association a(HBP:"Braak_Stage I") View Subject | View Object

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MeSH
Hippocampus

a(HBP:"Tau oligomers") association a(HBP:"Braak_Stage II") View Subject | View Object

Appears in Networks:
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MeSH
Hippocampus

p(HGNC:MAPT) association a(HBP:pretangles) View Subject | View Object

Appears in Networks:
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MeSH
Hippocampus

a(HBP:"phosphatase-activating domain") association a(HBP:pretangles) View Subject | View Object

Appears in Networks:
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MeSH
Hippocampus

a(HBP:"phosphatase-activating domain") association a(HBP:"Braak_Stage I") View Subject | View Object

Appears in Networks:
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MeSH
Hippocampus

a(HBP:"phosphatase-activating domain") association a(HBP:"Braak_Stage II") View Subject | View Object

Appears in Networks:
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MeSH
Hippocampus

a(HBP:pretangles) association a(HBP:"Tau oligomers") View Subject | View Object

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MeSH
Hippocampus

a(HBP:pretangles) association a(HBP:"phosphatase-activating domain") View Subject | View Object

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MeSH
Hippocampus

a(HBP:pretangles) association p(HGNC:MAPT) View Subject | View Object

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MeSH
Hippocampus

p(HGNC:MAPT) association a(HBP:"Braak_Stage I") View Subject | View Object

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MeSH
Hippocampus

p(HGNC:MAPT) association a(HBP:"Braak_Stage II") View Subject | View Object

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MeSH
Hippocampus

Evidence 485345f531
JSON

Similarly, the soluble fraction from AD contained the greatest level of TOC1 reactivity, followed by CBD and then PiD had the lowest signal (Fig. 6D; one-way ANOVA with Holm-Sidak post-hoc, F(2,9) = 16.57, p = 0.001)

a(HBP:"Corticobasal Degeneration") positiveCorrelation a(HBP:"Tau oligomers") View Subject | View Object

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a(HBP:"Tau oligomers") positiveCorrelation a(HBP:"Corticobasal Degeneration") View Subject | View Object

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a(HBP:"Tau oligomers") positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

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a(HBP:"Tau oligomers") positiveCorrelation path(MESH:"Pick Disease of the Brain") View Subject | View Object

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path(MESH:"Alzheimer Disease") positiveCorrelation a(HBP:"Tau oligomers") View Subject | View Object

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path(MESH:"Pick Disease of the Brain") positiveCorrelation a(HBP:"Tau oligomers") View Subject | View Object

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Evidence ee287cded7
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TOC1 detected significantly more oligomeric tau in AD compared to CBD and PiD and more in CBD compared to PiD (Fig. 6G; one-way ANOVA with Holm-Sidak post-hoc, F(2,9) = 35.32, p < 0.0001)

a(HBP:"Corticobasal Degeneration") positiveCorrelation a(HBP:"Tau oligomers") View Subject | View Object

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a(HBP:"Tau oligomers") positiveCorrelation a(HBP:"Corticobasal Degeneration") View Subject | View Object

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a(HBP:"Tau oligomers") positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

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a(HBP:"Tau oligomers") positiveCorrelation path(MESH:"Pick Disease of the Brain") View Subject | View Object

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path(MESH:"Alzheimer Disease") positiveCorrelation a(HBP:"Tau oligomers") View Subject | View Object

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path(MESH:"Pick Disease of the Brain") positiveCorrelation a(HBP:"Tau oligomers") View Subject | View Object

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Evidence cae734cb87
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In contrast, AD soluble tau displayed the highest level of TNT1 followed by CBD, with PiD having the lowest levels (Fig. 6C; one-way ANOVA with Holm-Sidak post-hoc, F(2,9) = 24.87, p = 0.0002).

a(HBP:"Corticobasal Degeneration") positiveCorrelation a(HBP:"phosphatase-activating domain") View Subject | View Object

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a(HBP:"phosphatase-activating domain") positiveCorrelation a(HBP:"Corticobasal Degeneration") View Subject | View Object

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a(HBP:"phosphatase-activating domain") positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

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a(HBP:"phosphatase-activating domain") positiveCorrelation path(MESH:"Pick Disease of the Brain") View Subject | View Object

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path(MESH:"Alzheimer Disease") positiveCorrelation a(HBP:"phosphatase-activating domain") View Subject | View Object

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path(MESH:"Pick Disease of the Brain") positiveCorrelation a(HBP:"phosphatase-activating domain") View Subject | View Object

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Evidence f8a18cd251
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Total tau levels in the soluble fractions were similar for AD, CBD and PiD, as indicated by the Tau5 sandwich ELISA (Fig. 6B; one-way ANOVA, F(2,9) = 3.283, p = 0.085)

a(HBP:"Corticobasal Degeneration") positiveCorrelation p(HGNC:MAPT) View Subject | View Object

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p(HGNC:MAPT) positiveCorrelation a(HBP:"Corticobasal Degeneration") View Subject | View Object

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p(HGNC:MAPT) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

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p(HGNC:MAPT) positiveCorrelation path(MESH:"Pick Disease of the Brain") View Subject | View Object

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path(MESH:"Alzheimer Disease") positiveCorrelation p(HGNC:MAPT) View Subject | View Object

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path(MESH:"Pick Disease of the Brain") positiveCorrelation p(HGNC:MAPT) View Subject | View Object

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Evidence 4ce1ea6638
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Total tau levels in the insoluble fractions, as detected by Tau5, were highest in AD, followed by CBD and PiD contained the least (Fig. 6E; one-way ANOVA with Holm-Sidak post-hoc, F(2,9) = 25.93, p = 0.0002)

a(HBP:"Corticobasal Degeneration") positiveCorrelation p(HGNC:MAPT) View Subject | View Object

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p(HGNC:MAPT) positiveCorrelation a(HBP:"Corticobasal Degeneration") View Subject | View Object

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p(HGNC:MAPT) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

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p(HGNC:MAPT) positiveCorrelation path(MESH:"Pick Disease of the Brain") View Subject | View Object

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path(MESH:"Alzheimer Disease") positiveCorrelation p(HGNC:MAPT) View Subject | View Object

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path(MESH:"Pick Disease of the Brain") positiveCorrelation p(HGNC:MAPT) View Subject | View Object

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Evidence 21c65fff02
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TNT1 detected significantly more PAD exposed tau in AD compared to PiD, and more in CBD when compared to PiD, but AD and CBD were not different (Fig. 6F; one-way ANOVA with Holm-Sidak post-hoc, F(2,9) = 12.07, p = 0.0028)

a(HBP:"Corticobasal Degeneration") positiveCorrelation composite(a(HBP:"phosphatase-activating domain"), p(HGNC:MAPT)) View Subject | View Object

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composite(a(HBP:"phosphatase-activating domain"), p(HGNC:MAPT)) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

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composite(a(HBP:"phosphatase-activating domain"), p(HGNC:MAPT)) positiveCorrelation path(MESH:"Pick Disease of the Brain") View Subject | View Object

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composite(a(HBP:"phosphatase-activating domain"), p(HGNC:MAPT)) positiveCorrelation a(HBP:"Corticobasal Degeneration") View Subject | View Object

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path(MESH:"Alzheimer Disease") positiveCorrelation composite(a(HBP:"phosphatase-activating domain"), p(HGNC:MAPT)) View Subject | View Object

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path(MESH:"Pick Disease of the Brain") positiveCorrelation composite(a(HBP:"phosphatase-activating domain"), p(HGNC:MAPT)) View Subject | View Object

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Evidence d018bbd104
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Collectively, these studies indicate that inhibition of anterograde FAT represents a toxic effect common to all tau aggregates, regardless of isoform composition

a(HBP:"Tau aggregates") decreases bp(GO:"anterograde axonal transport") View Subject | View Object

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Evidence 170ed7155e
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As expected, monomer and aggregated samples of all six tau isoforms showed equal reactivity for TNT1 and TOC1 when the samples were denatured because this exposes the epitopes making them equally accessible (Student’s t-tests, for all comparisons p > 0.05; Fig. 3C–H)

a(HBP:"Tau isoform B (381 aa)") increases a(HBP:"Tau oligomers") View Subject | View Object

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a(HBP:"Tau isoform B (381 aa)") positiveCorrelation a(HBP:"phosphatase-activating domain") View Subject | View Object

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a(HBP:"Tau isoform C (410 aa)") positiveCorrelation a(HBP:"phosphatase-activating domain") View Subject | View Object

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a(HBP:"Tau isoform C (410 aa)") increases a(HBP:"Tau oligomers") View Subject | View Object

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a(HBP:"Tau isoform D (383 aa)") positiveCorrelation a(HBP:"phosphatase-activating domain") View Subject | View Object

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a(HBP:"Tau isoform D (383 aa)") increases a(HBP:"Tau oligomers") View Subject | View Object

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a(HBP:"Tau isoform E (412 aa)") increases a(HBP:"Tau oligomers") View Subject | View Object

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a(HBP:"Tau isoform E (412 aa)") positiveCorrelation a(HBP:"phosphatase-activating domain") View Subject | View Object

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a(HBP:"Tau isoform F (441 aa)") increases a(HBP:"Tau oligomers") View Subject | View Object

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a(HBP:"Tau isoform F (441 aa)") positiveCorrelation a(HBP:"phosphatase-activating domain") View Subject | View Object

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a(HBP:"Tau isoform Fetal-tau (352 aa)") positiveCorrelation a(HBP:"phosphatase-activating domain") View Subject | View Object

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a(HBP:"Tau isoform Fetal-tau (352 aa)") increases a(HBP:"Tau oligomers") View Subject | View Object

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a(HBP:"phosphatase-activating domain") positiveCorrelation a(HBP:"Tau isoform Fetal-tau (352 aa)") View Subject | View Object

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a(HBP:"phosphatase-activating domain") positiveCorrelation a(HBP:"Tau isoform D (383 aa)") View Subject | View Object

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a(HBP:"phosphatase-activating domain") positiveCorrelation a(HBP:"Tau isoform C (410 aa)") View Subject | View Object

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a(HBP:"phosphatase-activating domain") positiveCorrelation a(HBP:"Tau isoform B (381 aa)") View Subject | View Object

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a(HBP:"phosphatase-activating domain") positiveCorrelation a(HBP:"Tau isoform F (441 aa)") View Subject | View Object

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a(HBP:"phosphatase-activating domain") positiveCorrelation a(HBP:"Tau isoform E (412 aa)") View Subject | View Object

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p(HBP:"Tau isoform B (381 aa)", pmod(HBP:"protein aggregation")) increases a(HBP:"Tau oligomers") View Subject | View Object

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p(HBP:"Tau isoform C (410 aa)", pmod(HBP:"protein aggregation")) increases a(HBP:"Tau oligomers") View Subject | View Object

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p(HBP:"Tau isoform D (383 aa)", pmod(HBP:"protein aggregation")) increases a(HBP:"Tau oligomers") View Subject | View Object

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p(HBP:"Tau isoform E (412 aa)", pmod(HBP:"protein aggregation")) increases a(HBP:"Tau oligomers") View Subject | View Object

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p(HBP:"Tau isoform F (441 aa)", pmod(HBP:"protein aggregation")) increases a(HBP:"Tau oligomers") View Subject | View Object

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p(HBP:"Tau isoform Fetal-tau (352 aa)", pmod(HBP:"protein aggregation")) increases a(HBP:"Tau oligomers") View Subject | View Object

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Evidence d69a4ec043
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Comparisons between isoform monomers showed that hT39 monomer signal was significantly higher than hT24 and hT23 monomers (Kruskal-Wallis ANOVA with Dunn’s post-hoc, H = 18.4, p = 0.0025)

a(HBP:"Tau isoform C (410 aa)") association a(HBP:"phosphatase-activating domain") View Subject | View Object

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a(HBP:"Tau isoform D (383 aa)") association a(HBP:"phosphatase-activating domain") View Subject | View Object

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a(HBP:"Tau isoform Fetal-tau (352 aa)") association a(HBP:"phosphatase-activating domain") View Subject | View Object

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a(HBP:"phosphatase-activating domain") association a(HBP:"Tau isoform Fetal-tau (352 aa)") View Subject | View Object

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a(HBP:"phosphatase-activating domain") association a(HBP:"Tau isoform D (383 aa)") View Subject | View Object

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a(HBP:"phosphatase-activating domain") association a(HBP:"Tau isoform C (410 aa)") View Subject | View Object

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Evidence 6555467b8b
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Comparisons between isoform monomers showed that hT39 monomer signal was significantly higher than hT24 and hT23 monomers (Kruskal-Wallis ANOVA with Dunn’s post-hoc, H = 18.6, p = 0.0023)

a(HBP:"Tau isoform C (410 aa)") increases a(HBP:"Tau oligomers") View Subject | View Object

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a(HBP:"Tau isoform D (383 aa)") increases a(HBP:"Tau oligomers") View Subject | View Object

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a(HBP:"Tau isoform Fetal-tau (352 aa)") increases a(HBP:"Tau oligomers") View Subject | View Object

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Evidence 97c382ea0c
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hT40 showed the highest amount of light scattering compared to other 4R isoforms, and there were no differences between the different 3R isoforms

a(HBP:"Tau isoform F (441 aa)") positiveCorrelation path(MESH:"Protein Aggregation, Pathological") View Subject | View Object

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path(MESH:"Protein Aggregation, Pathological") positiveCorrelation a(HBP:"Tau isoform F (441 aa)") View Subject | View Object

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Evidence f66d1c82bb
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In severe AD cases (i.e. Braak stage V-VI), all markers continue to colocalize in classic NFTs within the hippocampus that characterize AD tau pathology (Fig. 5E–H)

a(HBP:"Tau oligomers") association a(MESH:"Neurofibrillary Tangles") View Subject | View Object

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Annotations
MeSH
Hippocampus
MeSH
Alzheimer Disease

a(HBP:"phosphatase-activating domain") association a(MESH:"Neurofibrillary Tangles") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Hippocampus
MeSH
Alzheimer Disease

a(MESH:"Neurofibrillary Tangles") association a(HBP:"Tau oligomers") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Hippocampus
MeSH
Alzheimer Disease

a(MESH:"Neurofibrillary Tangles") association a(HBP:"phosphatase-activating domain") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Hippocampus
MeSH
Alzheimer Disease

a(MESH:"Neurofibrillary Tangles") association p(HGNC:MAPT) View Subject | View Object

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Annotations
MeSH
Hippocampus
MeSH
Alzheimer Disease

p(HGNC:MAPT) association a(MESH:"Neurofibrillary Tangles") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Hippocampus
MeSH
Alzheimer Disease

Evidence a524a126a1
JSON

In general, the remarkable co-localization between TNT1, TOC1 and R1 in all tauopathies confirms that PAD exposure and tau oligomerization occur simultaneously in cells displaying tau pathology, irrespective of isoform composition

a(HBP:"Tau oligomers") positiveCorrelation path(MESH:Tauopathies) View Subject | View Object

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a(HBP:"phosphatase-activating domain") positiveCorrelation path(MESH:Tauopathies) View Subject | View Object

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path(MESH:Tauopathies) positiveCorrelation a(HBP:"Tau oligomers") View Subject | View Object

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path(MESH:Tauopathies) positiveCorrelation a(HBP:"phosphatase-activating domain") View Subject | View Object

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Evidence 83af072875
JSON

The hT24 aggregates showed the highest TNT1 signal, which reached significance compared to hT40, hT39, hT37 and hT23 aggregates (one-way ANOVA with Holm-Sidak post-hoc, F(5, 18) = 19.11, p < 0.0001)

a(HBP:"phosphatase-activating domain") positiveCorrelation p(HBP:"Tau isoform D (383 aa)", pmod(HBP:"protein aggregation")) View Subject | View Object

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a(HBP:"phosphatase-activating domain") positiveCorrelation p(HBP:"Tau isoform C (410 aa)", pmod(HBP:"protein aggregation")) View Subject | View Object

Appears in Networks:

a(HBP:"phosphatase-activating domain") positiveCorrelation p(HBP:"Tau isoform Fetal-tau (352 aa)", pmod(HBP:"protein aggregation")) View Subject | View Object

Appears in Networks:

a(HBP:"phosphatase-activating domain") positiveCorrelation p(HBP:"Tau isoform B (381 aa)", pmod(HBP:"protein aggregation")) View Subject | View Object

Appears in Networks:

a(HBP:"phosphatase-activating domain") positiveCorrelation p(HBP:"Tau isoform F (441 aa)", pmod(HBP:"protein aggregation")) View Subject | View Object

Appears in Networks:

p(HBP:"Tau isoform B (381 aa)", pmod(HBP:"protein aggregation")) positiveCorrelation a(HBP:"phosphatase-activating domain") View Subject | View Object

Appears in Networks:

p(HBP:"Tau isoform C (410 aa)", pmod(HBP:"protein aggregation")) positiveCorrelation a(HBP:"phosphatase-activating domain") View Subject | View Object

Appears in Networks:

p(HBP:"Tau isoform D (383 aa)", pmod(HBP:"protein aggregation")) positiveCorrelation a(HBP:"phosphatase-activating domain") View Subject | View Object

Appears in Networks:

p(HBP:"Tau isoform F (441 aa)", pmod(HBP:"protein aggregation")) positiveCorrelation a(HBP:"phosphatase-activating domain") View Subject | View Object

Appears in Networks:

p(HBP:"Tau isoform Fetal-tau (352 aa)", pmod(HBP:"protein aggregation")) positiveCorrelation a(HBP:"phosphatase-activating domain") View Subject | View Object

Appears in Networks:

Evidence dd9a0c4b36
JSON

Aggregates of all six tau isoforms showed significant increases in TNT1 reactivity when compared to their respective monomer samples (Fig. 3A; Mann-Whitney test, for all comparisons p = 0.029)

a(HBP:"phosphatase-activating domain") positiveCorrelation p(HBP:"Tau isoform D (383 aa)", pmod(HBP:"protein aggregation")) View Subject | View Object

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a(HBP:"phosphatase-activating domain") positiveCorrelation p(HBP:"Tau isoform C (410 aa)", pmod(HBP:"protein aggregation")) View Subject | View Object

Appears in Networks:

a(HBP:"phosphatase-activating domain") positiveCorrelation p(HBP:"Tau isoform Fetal-tau (352 aa)", pmod(HBP:"protein aggregation")) View Subject | View Object

Appears in Networks:

a(HBP:"phosphatase-activating domain") positiveCorrelation p(HBP:"Tau isoform B (381 aa)", pmod(HBP:"protein aggregation")) View Subject | View Object

Appears in Networks:

a(HBP:"phosphatase-activating domain") positiveCorrelation p(HBP:"Tau isoform F (441 aa)", pmod(HBP:"protein aggregation")) View Subject | View Object

Appears in Networks:

a(HBP:"phosphatase-activating domain") positiveCorrelation p(HBP:"Tau isoform E (412 aa)", pmod(HBP:"protein aggregation")) View Subject | View Object

Appears in Networks:

p(HBP:"Tau isoform B (381 aa)", pmod(HBP:"protein aggregation")) positiveCorrelation a(HBP:"phosphatase-activating domain") View Subject | View Object

Appears in Networks:

p(HBP:"Tau isoform C (410 aa)", pmod(HBP:"protein aggregation")) positiveCorrelation a(HBP:"phosphatase-activating domain") View Subject | View Object

Appears in Networks:

p(HBP:"Tau isoform D (383 aa)", pmod(HBP:"protein aggregation")) positiveCorrelation a(HBP:"phosphatase-activating domain") View Subject | View Object

Appears in Networks:

p(HBP:"Tau isoform E (412 aa)", pmod(HBP:"protein aggregation")) positiveCorrelation a(HBP:"phosphatase-activating domain") View Subject | View Object

Appears in Networks:

p(HBP:"Tau isoform F (441 aa)", pmod(HBP:"protein aggregation")) positiveCorrelation a(HBP:"phosphatase-activating domain") View Subject | View Object

Appears in Networks:

p(HBP:"Tau isoform Fetal-tau (352 aa)", pmod(HBP:"protein aggregation")) positiveCorrelation a(HBP:"phosphatase-activating domain") View Subject | View Object

Appears in Networks:

Evidence 732a69709b
JSON

The hT24 aggregates showed the highest TOC1 signal, which reached significance compared to hT40, hT39, hT37 and hT23 aggregates, while hT34 aggregates were significantly different from hT39, hT37 and hT23 aggregates, and both hT40 and hT39 aggregates are significantly higher than hT37 and hT23 (one-way ANOVA with Holm-Sidak post-hoc, F(5, 18) = 50.77, p < 0.0001)

p(HBP:"Tau isoform B (381 aa)", pmod(HBP:"protein aggregation")) increases a(HBP:"Tau oligomers") View Subject | View Object

Appears in Networks:

p(HBP:"Tau isoform C (410 aa)", pmod(HBP:"protein aggregation")) increases a(HBP:"Tau oligomers") View Subject | View Object

Appears in Networks:

p(HBP:"Tau isoform D (383 aa)", pmod(HBP:"protein aggregation")) increases a(HBP:"Tau oligomers") View Subject | View Object

Appears in Networks:

p(HBP:"Tau isoform E (412 aa)", pmod(HBP:"protein aggregation")) increases a(HBP:"Tau oligomers") View Subject | View Object

Appears in Networks:

p(HBP:"Tau isoform F (441 aa)", pmod(HBP:"protein aggregation")) increases a(HBP:"Tau oligomers") View Subject | View Object

Appears in Networks:

p(HBP:"Tau isoform Fetal-tau (352 aa)", pmod(HBP:"protein aggregation")) increases a(HBP:"Tau oligomers") View Subject | View Object

Appears in Networks:

Evidence 5fbbd6a350
JSON

Aggregated samples for all six isoforms showed significant increases in TOC1 reactivity when compared to their respective monomer samples (Fig. 3B; Mann-Whitney tests, for all comparisons p = 0.029)

p(HBP:"Tau isoform B (381 aa)", pmod(HBP:"protein aggregation")) increases a(HBP:"Tau oligomers") View Subject | View Object

Appears in Networks:

p(HBP:"Tau isoform C (410 aa)", pmod(HBP:"protein aggregation")) increases a(HBP:"Tau oligomers") View Subject | View Object

Appears in Networks:

p(HBP:"Tau isoform D (383 aa)", pmod(HBP:"protein aggregation")) increases a(HBP:"Tau oligomers") View Subject | View Object

Appears in Networks:

p(HBP:"Tau isoform E (412 aa)", pmod(HBP:"protein aggregation")) increases a(HBP:"Tau oligomers") View Subject | View Object

Appears in Networks:

p(HBP:"Tau isoform F (441 aa)", pmod(HBP:"protein aggregation")) increases a(HBP:"Tau oligomers") View Subject | View Object

Appears in Networks:

p(HBP:"Tau isoform Fetal-tau (352 aa)", pmod(HBP:"protein aggregation")) increases a(HBP:"Tau oligomers") View Subject | View Object

Appears in Networks:

Evidence 011a4a46e5
JSON

Similarly, perfusion of squid axoplasms with hT39, hT37 and hT23 aggregates significantly impaired anterograde FAT (Fig. 4A) when compared to the respective monomers (all at 2 μM)

p(HBP:"Tau isoform B (381 aa)", pmod(HBP:"protein aggregation")) decreases bp(GO:"anterograde axonal transport") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Axons
MeSH
Cytoplasm

p(HBP:"Tau isoform C (410 aa)", pmod(HBP:"protein aggregation")) decreases bp(GO:"anterograde axonal transport") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Axons
MeSH
Cytoplasm

p(HBP:"Tau isoform Fetal-tau (352 aa)", pmod(HBP:"protein aggregation")) decreases bp(GO:"anterograde axonal transport") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Axons
MeSH
Cytoplasm

Evidence cc8efef072
JSON

hT40, hT34, hT24, hT37 and hT23 aggregates did not significantly impair retrograde FAT when compared to the respective monomers, but hT39 aggregates elicited a mild inhibitory effect on retrograde FAT (Fig. 4B)

p(HBP:"Tau isoform B (381 aa)", pmod(HBP:"protein aggregation")) causesNoChange bp(GO:"retrograde axonal transport") View Subject | View Object

Appears in Networks:

p(HBP:"Tau isoform C (410 aa)", pmod(HBP:"protein aggregation")) decreases bp(GO:"retrograde axonal transport") View Subject | View Object

Appears in Networks:

p(HBP:"Tau isoform D (383 aa)", pmod(HBP:"protein aggregation")) causesNoChange bp(GO:"retrograde axonal transport") View Subject | View Object

Appears in Networks:

p(HBP:"Tau isoform E (412 aa)", pmod(HBP:"protein aggregation")) causesNoChange bp(GO:"retrograde axonal transport") View Subject | View Object

Appears in Networks:

p(HBP:"Tau isoform F (441 aa)", pmod(HBP:"protein aggregation")) causesNoChange bp(GO:"retrograde axonal transport") View Subject | View Object

Appears in Networks:

p(HBP:"Tau isoform Fetal-tau (352 aa)", pmod(HBP:"protein aggregation")) causesNoChange bp(GO:"retrograde axonal transport") View Subject | View Object

Appears in Networks:

Evidence c6b62bf3a3
JSON

Pairwise comparisons within tau species showed that hT24 aggregates produced significantly more inhibition of anterograde FAT when compared to hT34 and hT39 aggregates.

p(HBP:"Tau isoform C (410 aa)", pmod(HBP:"protein aggregation")) decreases bp(GO:"anterograde axonal transport") View Subject | View Object

Appears in Networks:

p(HBP:"Tau isoform D (383 aa)", pmod(HBP:"protein aggregation")) decreases bp(GO:"anterograde axonal transport") View Subject | View Object

Appears in Networks:

p(HBP:"Tau isoform E (412 aa)", pmod(HBP:"protein aggregation")) decreases bp(GO:"anterograde axonal transport") View Subject | View Object

Appears in Networks:

Evidence 31db411d19
JSON

Perfusion of hT40, hT34 and hT24 aggregates into squid axoplasms significantly impaired anterograde transport (Fig. 4A) when compared to the respective monomers (all at 2 μM).

p(HBP:"Tau isoform D (383 aa)", pmod(HBP:"protein aggregation")) decreases bp(GO:"anterograde axonal transport") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Axons
MeSH
Cytoplasm

p(HBP:"Tau isoform E (412 aa)", pmod(HBP:"protein aggregation")) decreases bp(GO:"anterograde axonal transport") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Axons
MeSH
Cytoplasm

p(HBP:"Tau isoform F (441 aa)", pmod(HBP:"protein aggregation")) decreases bp(GO:"anterograde axonal transport") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Axons
MeSH
Cytoplasm

Evidence 22919f6c23
JSON

Aggregation-induced increases in PAD exposure and oligomerization are common features among all tau isoforms. The extent of PAD exposure and oligomerization was larger for tau aggregates composed of 4-repeat isoforms compared with those made of 3-repeat isoforms.

p(HBP:"4R tau") positiveCorrelation p(HBP:"phosphatase-activating domain") View Subject | View Object

Appears in Networks:

p(HBP:"phosphatase-activating domain") positiveCorrelation p(HBP:"4R tau") View Subject | View Object

Appears in Networks:

About

BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.

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.