Biomedical Research Institute / Hasselt University
Department of Neurosciences

Presenter Of 1 Presentation

AMYLOID FACILITATED TAU-SEEDING AND SUBSEQUENT TAU-INDUCED NEURODEGENERATION: RECAPITULATING THE A/T/N-AXIS IN VIVO

Session Type
SYMPOSIUM
Date
Fri, 18.03.2022
Session Time
02:45 PM - 04:45 PM
Room
Onsite: 114
Lecture Time
03:00 PM - 03:15 PM

Abstract

Aims

Brains of AD patients are characterized by the presence of amyloid pathology, Tau-pathology and neurodegeneration, referred to as A-, T- and N-pathology respectively. These stages develop in a characteristic spatio-temporal way in AD patients. Previous publications demonstrated amyloid facilitated tau seeding of endogenous tau, highlighting the relevance of amyloid facilitated tau pathology. We now focused on the development of a preclinical model that recapitulates all aspects of ATN pathology, downstream of amyloid pathology.

Methods

Hereto, we analyzed the effect of amyloid pathology on Tau-seeded pathology, its propagation and subsequent neurodegeneration in crosses of TauP301S and 5xFAD mice.

Results

Tau-seeded Tau-pathology was significantly increased in the presence of amyloid pathology. Tau-pathology propagated more efficiently to functionally connected brain areas at the ipsi- and contralateral side, remote from the injection site in the presence of amyloid pathology. Most strikingly, in the presence of amyloid pathology, Tau-seeding induced significant hippocampal and cortical atrophy, correlating with the level of Tau-pathology. Finally, microgliosis significantly increased at the different stages of the ATN axis in this model.

Conclusions

Our in vivo model displays amyloid facilitated propagation of Tau-seeded pathology and Tau-induced neurodegeneration. We here present a model robustly recapitulating the ATN pathologies, providing a tool to gain mechanistic insights in the interrelation and synergism between A, T and N pathologies to gain insight in the progressive development of ATN pathologies in AD.

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