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PubMed: 26671985

Title
Characterization of Early Pathological Tau Conformations and Phosphorylation in Chronic Traumatic Encephalopathy.
Journal
Journal of neuropathology and experimental neurology
Volume
75
Issue
None
Pages
19-34
Date
2016-01-01
Authors
Alvarez VE | Cox K | Kanaan NM | McKee AC | Poncil S | Stein TD

Evidence 0ff6e9d36b
JSON

Several lines of evidence in other tauopathies suggest that tau oligomer formation induces neurotoxicity and that tau oligomer-mediated neurotoxicity involves induction of axonal dysfunction through exposure of an N-terminal motif in tau, the phosphatase-activating domain (PAD).

act(a(HBP:"Tau oligomers")) decreases act(complex(GO:axon)) View Subject | View Object

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act(a(HBP:"Tau oligomers")) positiveCorrelation p(HBP:"phosphatase-activating domain") View Subject | View Object

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act(a(HBP:"Tau oligomers")) increases a(HBP:neurotoxicity) View Subject | View Object

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a(HBP:neurotoxicity) negativeCorrelation act(complex(GO:axon)) View Subject | View Object

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act(complex(GO:axon)) negativeCorrelation a(HBP:neurotoxicity) View Subject | View Object

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p(HBP:"phosphatase-activating domain") positiveCorrelation act(a(HBP:"Tau oligomers")) View Subject | View Object

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p(HBP:"phosphatase-activating domain") decreases act(complex(GO:axon)) View Subject | View Object

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Evidence 289c10601d
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We performed immunohistochemistry and immunofluorescence on fixed brain sections and biochemical analysis of fresh brain extracts to characterize the presence of PAD-exposed tau (TNT1 antibody), tau oligomers (TOC1 antibody), tau phosphorylated at S422 (pS422 antibody), and tau truncated at D421 (TauC3 antibody) in the brains of 9-11 cases with CTE and cases of nondemented aged controls and AD (Braak VI) (n = 6, each). These 4 markers are particularly useful in understanding potential posttraumatic events in CTE because PAD exposure impairs axonal transport (24), oligomers confer toxicity (28, 38–40), pS422 correlates with cognitive decline (15), and D421 truncated tau may be related to cell toxicity (41, 42). All 3 early tau markers (ie, TNT1, TOC1, and pS422) were present in CTE and displayed extensive colocalization in perivascular tau lesions that are considered diagnostic for CTE.

p(HBP:"phosphatase-activating domain") biomarkerFor path(MESH:"Chronic Traumatic Encephalopathy") View Subject | View Object

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Annotations
MeSH
Chronic Traumatic Encephalopathy

p(HBP:"phosphatase-activating domain") decreases bp(GO:"axonal transport") View Subject | View Object

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Annotations
MeSH
Chronic Traumatic Encephalopathy

p(HBP:neurotoxicity) positiveCorrelation p(HGNC:MAPT, var("p.Asp421*")) View Subject | View Object

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MeSH
Chronic Traumatic Encephalopathy

p(HGNC:MAPT, pmod(Ph, Ser, 422)) biomarkerFor path(MESH:"Chronic Traumatic Encephalopathy") View Subject | View Object

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MeSH
Chronic Traumatic Encephalopathy

p(HGNC:MAPT, pmod(Ph, Ser, 422)) increases path(MESH:"Cognitive Dysfunction") View Subject | View Object

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Annotations
MeSH
Chronic Traumatic Encephalopathy

p(HGNC:MAPT, var("p.Asp421*")) biomarkerFor path(MESH:"Chronic Traumatic Encephalopathy") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Chronic Traumatic Encephalopathy

p(HGNC:MAPT, var("p.Asp421*")) positiveCorrelation p(HBP:neurotoxicity) View Subject | View Object

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Annotations
MeSH
Chronic Traumatic Encephalopathy

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