PubMed: 25887395

Tau Trimers Are the Minimal Propagation Unit Spontaneously Internalized to Seed Intracellular Aggregation.
The Journal of biological chemistry
Bieschke J | Diamond MI | Holmes BB | Mirbaha H | Sanders DW

Evidence 3ca4f53654

Heparin blocks Tau binding by masking HSPG binding sites on Tau, and sodium chlorate inhibits HSPG sulfation.

Evidence 89b13a905e

To test whether HSPGs also mediate BD Tau seeding, we titrated heparin and sodium chlorate, which inhibited seeding of all species (Fig. 8D).

Evidence fe32196adc

Whereas control brain homogenate exhibited mainly Tau monomer, the AD brain contained a range of Tau assemblies ranging from n = 1 to n > 20 (Fig. 7, A and B).

Evidence 6d3b361f2d

Heparan sulfate proteoglycans (HSPGs) are cell surface pro- teins that bind Tau fibrils and are required for their uptake and seeding (10).

Evidence c51d6f250b

Within the limits of our detection, neither monomer nor dimer was internalized (Fig. 5, A and B). By contrast, trimers and larger species were readily internalized, with trimer uptake being slightly less efficient (Fig. 5, A and B). We did not observe an upper limit of size in terms of uptake.

Evidence b5760ee55e

Only Tau RD oligomers of n  3 increased luciferase signal, defining these assemblies as the minimal size sufficient for spontaneous cell uptake and seeding (Fig. 6C).

Evidence d1e83a3838

Next we analyzed fractions for seeding activity in the P301S- Nluc/Cluc HEK293 cell lines by a split-luciferase complemen- tation assay, comparing AD and control brains. Trimers and larger BD Tau assemblies induced intracellular aggregation, but not monomer or dimer.

Evidence f322b280a1

Tau RD fibrillizes very efficiently in vitro, making it ideal for fundamental studies (13).


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