ArticleThe EMBO journal2025
Tau uptake by human neurons depends on receptor LRP1 and kinase LRRK2.
Article in The EMBO journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- High-Throughput Screening Identifies Small-Molecule Inhibitors of the Tau-LRP1 Interaction.bioRxiv : the preprint server for biology · 2026Article
- Article
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- Biomarkers of Leucine-Rich Repeat Kinase 2 (LRRK2) and Lysosomal Dysfunction in Progressive Supranuclear Palsy.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Tracking tau and cellular responses in human iPSC-microglia: from uptake to seedable secretion, including in extracellular vesicles.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- LRRK2 kinase-mediated accumulation of lysosome-associated phospho-Rabs in tauopathies and synucleinopathies.Acta neuropathologica · 2025Article
- A phenotypic screen for novel small molecules that correct tau-mediated pathologies in human frontotemporal dementia neurons.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
Corrections and comments
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Authors and funding
14 authors.
Funding
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 neuronal surface: the low-density lipoprotein LRP1 is the primary receptor for monomeric tau, but contributes less to fibrillar tau entry. Similarly, endocytosis of monomeric tau is dependent on the familial Parkinson's disease gene LRRK2, but not required for endocytosis of fibrillar tau. These findings implicate LRP1 and LRRK2 in the pathogenesis of tauopathies and Parkinson's disease, and identify LRRK2 as a potential therapeutic target for altering progression of these diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.