From the prion-like propagation hypothesis to therapeutic strategies of anti-tau immunotherapy

Abstract : The term “propagon” is used to define proteins that may transmit misfolding in vitro, in tissues or in organisms. Among propagons, misfolded tau is thought to be involved in the pathogenic mechanisms of various “tauopathies” that include Alzheimer’s disease, progressive supranuclear palsy, and argyrophilic grain disease. Here, we review the available data in the literature and point out how the prion-like tau propagation has been extended from Alzheimer’s disease to tauopathies. First, in Alzheimer’s disease, the progression of tau aggregation follows stereotypical anatomical stages which may be considered as spreading. The mechanisms of the propagation are now subject to intensive and controversial research. It has been shown that tau may be secreted in the interstitial fluid in an active manner as reflected by high and constant concentration of extracellular tau during Alzheimer’s pathology. Animal and cell models have been devised to mimic tau seeding and propagation, and despite their limitations, they have further supported to the prion-like propagation hypothesis. Finally, such new ways of thinking have led to different therapeutic strategies in anti-tau immunotherapy among tauopathies and have stimulated new clinical trials. However, it appears that the prion-like propagation hypothesis mainly relies on data obtained in Alzheimer’s disease. From this review, it appears that further studies are needed (1) to characterize extracellular tau species, (2) to find the right pathological tau species to target, (3) to follow in vivo tau pathology by brain imaging and biomarkers and (4) to interpret current clinical trial results aimed at reducing the progression of these pathologies. Such inputs will be essential to have a comprehensive view of these promising therapeutic strategies in tauopathies.
Complete list of metadatas

Cited literature [173 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-02348330
Contributor : Luc Buee <>
Submitted on : Tuesday, November 5, 2019 - 1:12:40 PM
Last modification on : Wednesday, November 6, 2019 - 1:47:43 AM

File

10.1007_s00401-019-02087-9.pdf
Publication funded by an institution

Identifiers

Citation

Morvane Colin, Simon Dujardin, Susanna Schraen-Maschke, Guy Meno-Tetang, Charles Duyckaerts, et al.. From the prion-like propagation hypothesis to therapeutic strategies of anti-tau immunotherapy. Acta Neuropathologica, Springer Verlag, 2019, Epub ahead of print. ⟨10.1007/s00401-019-02087-9⟩. ⟨inserm-02348330⟩

Share

Metrics

Record views

13

Files downloads

18