Monomeric tau uptake by human neurons depends on receptor LRP1 and kinase LRRK2

ABSTRACT: Extracellular release and uptake of pathogenic forms of the microtubule-associated protein tau contribute to the pathogenesis of several neurodegenerative diseases, including Alzheimer's disease. Defining the cellular mechanisms and pathways for tau entry to human neurons is essential to understanding tauopathy pathogenesis and enabling the rational design of disease-modifying therapeutics. Here, whole-genome, loss-of-function CRISPR screens in human iPSC-derived excitatory neurons, the major neuronal cell type affected in these diseases, provide insights into the different cellular pathways for uptake of extracellular monomeric and fibrillar tau. Monomeric and fibrillar tau are both taken up by human neurons by receptor-mediated endocytosis, but involve different routes of entry at the ne

SUBMITTER: Lewis, D Evans 

PROVIDER: S-SCDT-10_1038-S44318-025-00514-0 | biostudies-other |

REPOSITORIES: biostudies-other