1. Catalog
  2. Citations
  3. PubMed:26458742

PubMed: 26458742

Title
Neuronal uptake and propagation of a rare phosphorylated high-molecular-weight tau derived from Alzheimer's disease brain.
Journal
Nature communications
Volume
6
Issue
None
Pages
8490
Date
2015-10-13
Authors
Nobuhara CK | Takeda S | Carlson GA | Commins C | Costantino I | DeVos SL | Frosch MP | Hyman BT | Pitstick R | Roe AD | Wegmann S | Cho H | Irimia D | Müller DJ | Nicholls SB

Evidence 1d47810fa8
JSON

Phosphatase treatment dephosphorylated tau in rTg4510 brain extract (Fig. 7d) without changing HMW tau levels (Fig. 7e), resulting in a significant reduction of cellular uptake of tau (Fig. 7f).

p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) increases tloc(p(HGNC:MAPT), fromLoc(MESH:"Extracellular Space"), toLoc(MESH:"Intracellular Space")) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Brain

Evidence 55dc2f8ac3
JSON

Importantly, neuronal uptake of HMW tau occurred in vivo as well; human tau uptake in neurons was detected in young rTg4510 (pre-tangle stage) (Fig. 1j–l) and WT (Supplementary Fig. 6) mice injected with the HMW SEC fraction of Tg4510 (12 months) brain extract, but not in those injected with the LMW fractions.

a(HBP:HBP00006) increases tloc(p(HGNC:MAPT), fromLoc(MESH:"Extracellular Space"), toLoc(MESH:Neurons)) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High

Evidence f79e699093
JSON

There was no difference in cell viability between tau-aggregate positive and negative cells for up to 4 days (Supplementary Fig. 10).

a(HBP:HBP00006) causesNoChange bp(GO:"cell death") View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Brain

Evidence 4ea1e17ad7
JSON

The PBS- extractable tau species from rTg4510 brain had higher levels of phosphorylation compared with the tau species obtained from rTg21221, especially those associated with some specific phosphorylation sites such as pT205, pS262, pS400, pS404, pS409 and pS422.

p(HBP:HBP00056, var("p.Pro301Leu")) increases p(HBP:HBP00056, pmod(Ph, Thr, 205)) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium

p(HBP:HBP00056, var("p.Pro301Leu")) increases p(HBP:HBP00056, pmod(Ph, Ser, 262)) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium

p(HBP:HBP00056, var("p.Pro301Leu")) increases p(HBP:HBP00056, pmod(Ph, Ser, 400)) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium

p(HBP:HBP00056, var("p.Pro301Leu")) increases p(HBP:HBP00056, pmod(Ph, Ser, 404)) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium

p(HBP:HBP00056, var("p.Pro301Leu")) increases p(HBP:HBP00056, pmod(Ph, Ser, 409)) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium

p(HBP:HBP00056, var("p.Pro301Leu")) increases p(HBP:HBP00056, pmod(Ph, Ser, 422)) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium

Evidence f9db7d98f7
JSON

SEC analysis of the molecular weight distribution of tau demonstrated that rTg21221 brain extracts (PBS-soluble, 3,000g) contained primarily LMW species and very low levels of HMW tau species, whereas rTg4510 brain extract showed both HMW and LMW peaks (Fig. 2e,f).

p(HBP:HBP00056, var("p.Pro301Leu")) increases a(HBP:HBP00006) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium

Evidence 7bfc3baff6
JSON

The HMW tau species from the AD brain were highly phosphorylated compared with those from control brain (Fig. 6m).

p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) increases a(HBP:HBP00006) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Brain

Evidence de5366ace5
JSON

However, the AD brain extract (3,000g) contained significantly higher levels of phosphorylated tau (Fig. 6h,i,m) when compared with the control brain, especially those associated with some specific phosphorylation sites such as pS199, pS396 and pS404 (Fig. 6i).

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

Appears in Networks:
Annotations
Confidence
High
MeSH
Brain

p(HGNC:MAPT, pmod(Ph, Ser, 199)) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Brain

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

Appears in Networks:
Annotations
Confidence
High
MeSH
Brain

p(HGNC:MAPT, pmod(Ph, Ser, 404)) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Brain

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

Appears in Networks:
Annotations
Confidence
High
MeSH
Brain

path(MESH:"Alzheimer Disease") positiveCorrelation p(HGNC:MAPT, pmod(Ph, Ser, 199)) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Brain

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

Appears in Networks:
Annotations
Confidence
High
MeSH
Brain

path(MESH:"Alzheimer Disease") positiveCorrelation p(HGNC:MAPT, pmod(Ph, Ser, 404)) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Brain

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.