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PubMed: 28408124

Title
Tau Antibody Targeting Pathological Species Blocks Neuronal Uptake and Interneuron Propagation of Tau in Vitro.
Journal
The American journal of pathology
Volume
187
Issue
None
Pages
1399-1412
Date
2017-06-01
Authors
Nobuhara CK | Takeda S | Bussiere T | Carlson GA | Cheung AE | Commins C | Costantino I | DeVos SL | Dunah AW | Frosch MP | Grimm J | Hock C | Hyman BT | Montrasio F | Moore BD | Nitsch RM | Pitstick R | Roe AD | Wegmann S | Weinreb PH | Wittmann M

Evidence 6168071f12
JSON

Among the seven antibodies, Tau13 and 6C5 most efficiently removed tau (>85% reduction) from rTg4510 brain extracts on immunodepletion (Figure 2A). HT7 showed an intermediate effect (72% reduction), whereas the other four antibodies (40E8, 4E4, p396, and Tau46) removed only a small fraction of tau (5.6%, 16.6%, 8.4%, and 18% reductions, respectively) (Figure 2A).

a(HBP:"Tau antibody, 40E8") decreases p(MGI:Mapt, loc(GO:cell)) View Subject | View Object

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Brain
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Tauopathies
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a(HBP:"Tau antibody, 4E4") decreases p(MGI:Mapt, loc(GO:cell)) View Subject | View Object

Appears in Networks:
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Brain
MeSH
Tauopathies
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a(HBP:"Tau antibody, 6C5") decreases p(MGI:Mapt, loc(GO:cell)) View Subject | View Object

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Brain
MeSH
Tauopathies
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a(HBP:"Tau antibody, HT7") decreases p(MGI:Mapt, loc(GO:cell)) View Subject | View Object

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Brain
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Tauopathies
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a(HBP:"Tau antibody, Tau-13") decreases p(MGI:Mapt, loc(GO:cell)) View Subject | View Object

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Brain
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Tauopathies
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a(HBP:"Tau antibody, pS396") decreases p(MGI:Mapt, loc(GO:cell)) View Subject | View Object

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Brain
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Tauopathies
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Evidence 258c27ef6e
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The 40E8, 4E4, and p396 antibodies also reduced neuronal tau uptake by 40% to 80%, despite their low-immunodepletion efficiency (Figure 2). This finding suggests that they interacted with tau species that are prone to cellular uptake, which account for only a small fraction of all soluble tau species in the brain extract. Notably, Tau46 had little effect on tau uptake (Figure 2, B and C).

a(HBP:"Tau antibody, 40E8") decreases tloc(p(MGI:Mapt), fromLoc(GO:"extracellular region"), toLoc(GO:intracellular)) View Subject | View Object

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MeSH
Brain
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Tauopathies
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a(HBP:"Tau antibody, 4E4") decreases tloc(p(MGI:Mapt), fromLoc(GO:"extracellular region"), toLoc(GO:intracellular)) View Subject | View Object

Appears in Networks:
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MeSH
Brain
MeSH
Tauopathies
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Results

a(HBP:"Tau antibody, pS396") decreases tloc(p(MGI:Mapt), fromLoc(GO:"extracellular region"), toLoc(GO:intracellular)) View Subject | View Object

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Brain
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Tauopathies
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Evidence df0afb5a99
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Tau13, 6C5, and HT7 efficiently depleted tau from the AD HMW fraction (97%, 82%, and 72%, respectively), whereas the other four antibodies (40E8, 4E4, p396, and Tau46) removed only a small fraction of tau (33%, 4.7%, 22%, and 21% reductions, respectively) (Figure 4A).

a(HBP:"Tau antibody, 40E8") decreases p(HGNC:MAPT, loc(GO:cell)) View Subject | View Object

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Alzheimer Disease
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a(HBP:"Tau antibody, 4E4") decreases p(HGNC:MAPT, loc(GO:cell)) View Subject | View Object

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Alzheimer Disease
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a(HBP:"Tau antibody, 6C5") decreases p(HGNC:MAPT, loc(GO:cell)) View Subject | View Object

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Alzheimer Disease
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Results

a(HBP:"Tau antibody, HT7") decreases p(HGNC:MAPT, loc(GO:cell)) View Subject | View Object

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Alzheimer Disease
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a(HBP:"Tau antibody, Tau-13") decreases p(HGNC:MAPT, loc(GO:cell)) View Subject | View Object

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Alzheimer Disease
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a(HBP:"Tau antibody, pS396") decreases p(HGNC:MAPT, loc(GO:cell)) View Subject | View Object

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Alzheimer Disease
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Evidence 978a2f439c
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In the tau uptake assay, 6C5 most effectively reduced tau uptake by immunodepletion (75% reduction) (Figure 4, B and C). Tau13 and HT7 showed intermediate effects (55% and 47% reductions, respectively) (Figure 4, B and C). The 40E8, p396, and 4E4 antibodies also reduced neuronal tau uptake (65%, 53%, and 47% reductions, respectively), despite their low immunodepletion efficiency (Figure 4).

a(HBP:"Tau antibody, 40E8") decreases tloc(p(HGNC:MAPT), fromLoc(GO:"extracellular region"), toLoc(GO:intracellular)) View Subject | View Object

Appears in Networks:
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Neurons
MeSH
Alzheimer Disease
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Results

a(HBP:"Tau antibody, 4E4") decreases tloc(p(HGNC:MAPT), fromLoc(GO:"extracellular region"), toLoc(GO:intracellular)) View Subject | View Object

Appears in Networks:
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MeSH
Neurons
MeSH
Alzheimer Disease
Text Location
Results

a(HBP:"Tau antibody, 6C5") decreases tloc(p(HGNC:MAPT), fromLoc(GO:"extracellular region"), toLoc(GO:intracellular)) View Subject | View Object

Appears in Networks:
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MeSH
Neurons
MeSH
Alzheimer Disease
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Results

a(HBP:"Tau antibody, HT7") decreases tloc(p(HGNC:MAPT), fromLoc(GO:"extracellular region"), toLoc(GO:intracellular)) View Subject | View Object

Appears in Networks:
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Neurons
MeSH
Alzheimer Disease
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a(HBP:"Tau antibody, Tau-13") decreases tloc(p(HGNC:MAPT), fromLoc(GO:"extracellular region"), toLoc(GO:intracellular)) View Subject | View Object

Appears in Networks:
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MeSH
Neurons
MeSH
Alzheimer Disease
Text Location
Results

a(HBP:"Tau antibody, pS396") decreases tloc(p(HGNC:MAPT), fromLoc(GO:"extracellular region"), toLoc(GO:intracellular)) View Subject | View Object

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Neurons
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Alzheimer Disease
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Evidence 7a592708f0
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for example, the two phosphorylation dependent tau antibodies (40E8 and p396) were the most efficient in the human AD case with the highest level of phosphorylated tau (1266). Both 6C5 and 40E8, shown to be most effective at reducing uptake from HMW human AD brainederived tau species (Figure 3, B and C), immunostained NFTs and neuritic plaques in postmortem human AD frontal cortex sections (Figure 6); 40E8 was somewhat more reactive to neuropil threads under the conditions used.

a(HBP:"Tau antibody, 40E8") decreases p(HGNC:MAPT) View Subject | View Object

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Alzheimer Disease
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a(HBP:"Tau antibody, 40E8") decreases p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

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Alzheimer Disease
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a(HBP:"Tau antibody, 6C5") decreases p(HGNC:MAPT) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease
Text Location
Results

a(HBP:"Tau antibody, pS396") decreases p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

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Alzheimer Disease
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Results

Evidence 96912a3de4
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Confocal FRET image analysis showed robust tau aggregation in primary neurons treated with control IgG-immunodepleted rTg4510 brain extracts (Figure 2, B and C).The 6C5 antibody most successfully reduced tau uptake by immunodepletion (>90% reduction), and Tau13 and HT7 showed intermediate effects (approximately 60% reductions) (Figure 2, B and C)

a(HBP:"Tau antibody, 6C5") decreases tloc(p(MGI:Mapt), fromLoc(GO:"extracellular region"), toLoc(GO:intracellular)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Tauopathies
Text Location
Results

a(HBP:"Tau antibody, HT7") decreases tloc(p(MGI:Mapt), fromLoc(GO:"extracellular region"), toLoc(GO:intracellular)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Tauopathies
Text Location
Results

a(HBP:"Tau antibody, Tau-13") decreases tloc(p(MGI:Mapt), fromLoc(GO:"extracellular region"), toLoc(GO:intracellular)) View Subject | View Object

Appears in Networks:
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MeSH
Brain
MeSH
Tauopathies
Text Location
Results

tloc(p(MGI:Mapt), fromLoc(GO:"extracellular region"), toLoc(GO:intracellular)) increases a(HBP:"Tau aggregates") View Subject | View Object

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Brain
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Tauopathies
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Evidence 48791869ab
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This result is consistent with the idea that the 6C5 antibody can slow tau uptake even after neurons have been exposed to the pathological tau and the uptake process initiated.

a(HBP:"Tau antibody, 6C5") decreases tloc(p(HGNC:MAPT), fromLoc(GO:"extracellular region"), toLoc(GO:intracellular)) View Subject | View Object

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MeSH
Alzheimer Disease
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Results

Evidence 010986ea3f
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Tau46 was the only antibody that did not show a statistically significant reduction in neuronal tau uptake (Figure 4, B and C). Tau46 bound with high apparent affinity to both recombinant and paired helical filament tau by ELISA (Table 2), demonstrating the binding of the antibody to full-length tau.

a(HBP:"Tau antibody, Tau46") causesNoChange tloc(p(HGNC:MAPT), fromLoc(GO:"extracellular region"), toLoc(GO:intracellular)) View Subject | View Object

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Alzheimer Disease
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a(HBP:"Tau antibody, Tau46") association p(HGNC:MAPT) View Subject | View Object

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Alzheimer Disease
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p(HGNC:MAPT) association a(HBP:"Tau antibody, Tau46") View Subject | View Object

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Alzheimer Disease
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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.