Age dependent trans-cellular propagation of human tau aggregates in Drosophila disease models

Tauopathies is a class of neurodegenerative disorders which involves the transformation of physiological tau into pathogenic tau. One of the prime causes reported to drive this conversion is tau hyperphosphorylation and the subsequent propagation of pathogenic protein aggregates across the nervous system. Although past attempts have been made to deduce the details of tau propagation, yet not much is known about its mechanism. A better understanding of this aspect of disease pathology can prove to be beneficial for the development of diagnostic and therapeutic approaches. For the first time, we demonstrate that the human tau possesses an intrinsic property to spread trans-cellularly in the fly nervous system irrespective of the tau allele or the neuronal tissue type. Aggregate migration restricted by targeted down-regulation of a specific kinase, elucidates the role of hyper-phosphorylation in its movement. On the contrary to the previous models, our study delivers an easy and rapid in-vivo model for comprehensive examination of tau migration pathology. Henceforth, the developed model would not only be immensely helpful in uncovering the mechanistic in-depths of tau propagation pathology but also aid in modifier and/or drug screening for amelioration of tauopathies.

Automated summary

Tauopathies involve the conversion of physiological tau into pathogenic tau due to hyperphosphorylation, leading to protein aggregates propagation in the nervous system. A study found that human tau possesses an intrinsic property to spread trans-cellularly in the fly nervous system, with aggregate migration restricted by targeted down-regulation of a specific kinase. This newly developed in-vivo model provides a rapid and easy approach for comprehensive examination of tau migration pathology, aiding in understanding the mechanistic in-depths and potential drug screening for tauopathies.