A novel <i>C. elegans</i> model for MAPT/Tau spreading reveals genes critical for endolysosomal integrity and seeded MAPT/Tau aggregation.

ABSTRACT: The spreading of MAPT/Tau pathology is closely associated with the progression of neurodegeneration and cognitive decline in Alzheimer disease and other tauopathies. A key event in this process is the rupture of endolysosomal vesicles following the intercellular transfer of MAPT/Tau aggregates, releasing the transferred MAPT/Tau species into the cytosol where they can promote the aggregation of endogenous MAPT/Tau. However, understanding of the cellular pathways involved in this process remains limited. In this study, we investigated cellular pathways that prevent endolysosomal vesicle rupture. We established a new C. elegans model of MAPT/Tau spreading by introducing an mCherry-labeled, disease-associated aggregation-prone fragment of human MAPT/Tau (F3ΔK281::mCh) into the six touc

SUBMITTER: Sandhof CA 

PROVIDER: S-EPMC12758218 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature