Novel model of secreted human tau protein reveals the impact of the abnormal N-glycosylation of tau on its aggregation propensity

Yelena Losev, Ashim Paul, Moran Frenkel-Pinter, Malak Abu-Hussein, Isam Khalaila, Ehud Gazit, Daniel Segal*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Alzheimer’s disease (AD) is the most common neurodegenerative disorder and has no disease-modifying treatment yet. The hallmarks of AD are two amyloidogenic proteins: tau and amyloid β (Aβ). Tau undergoes several posttranslational modifications, including N-glycosylation. Tau was reported to be N-glycosylated in AD brains, but not in healthy counterparts, which may affect AD etiology. Here, we aimed to examine the effect of N-glycosylation on aggregation propensity of tau. To that end, a novel SH-SY5Y cell-based model was generated in which recombinant human tau (htau) is forced to be secreted from the cells. Secreted htau was found to localize in the secretory pathway compartments and to undergo N-glycosylation. Following N-glycan cleavage of the secreted htau, various biophysical results collectively indicated that the untreated N-glycosylated secreted htau is markedly less aggregative, contains thinner and shorter fibrils, as compared to treated de-glycosylated secreted htau. This finding shows that N-glycans attached to htau may affect its aggregation. This could help to better understand the effect of N-glycosylated htau on AD progression.

Original languageAmerican English
Article number2254
JournalScientific Reports
Issue number1
StatePublished - 1 Dec 2019
Externally publishedYes

Bibliographical note

Funding Information:
The authors wish to acknowledge Prof. Itai Benhar (Tel Aviv University) and Prof. Eckhard Mandelkow (DZNE, Bonn, Germany) for help with plasmid vectors. We thank Dr. Merav Daniel Shmueli for important discussion. This research was partially supported by the Israel Ministry of Science and the RoseTrees Trust (to D.S).

Publisher Copyright:
© 2019, The Author(s).


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