Evidence map›Paper›PMID 40790356›Full record

ArticleThe EMBO journal2025

Tau uptake by human neurons depends on receptor LRP1 and kinase LRRK2.

Lewis D Evans, Alessio Strano, Eleanor Tuck, Ashley Campbell, James Smith, Christy Hung, Tiana S Behr, Bernardino Ghetti, Benjamin Ryskeldi-Falcon, Emre Karakoc and 4 more

Abstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Biomarkers of Leucine-Rich Repeat Kinase 2 (LRRK2) and Lysosomal Dysfunction in Progressive Supranuclear Palsy.Movement disorders : official journal of the Movement Disorder Society · 2026
    Article
  5. Article
  6. Article
  7. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Lewis D EvansUCL Great Ormond Street Institute of Child Health, Department of Developmental Biology and Cancer, Zayed Centre for Research into Rare Disease in Children, London, WC1N 1DZ, UK.ORCID http://orcid.org/0000-0001-7279-7651
Alessio StranoUCL Great Ormond Street Institute of Child Health, Department of Developmental Biology and Cancer, Zayed Centre for Research into Rare Disease in Children, London, WC1N 1DZ, UK.
Eleanor TuckUCL Great Ormond Street Institute of Child Health, Department of Developmental Biology and Cancer, Zayed Centre for Research into Rare Disease in Children, London, WC1N 1DZ, UK.
Ashley CampbellUCL Great Ormond Street Institute of Child Health, Department of Developmental Biology and Cancer, Zayed Centre for Research into Rare Disease in Children, London, WC1N 1DZ, UK.
James SmithUCL Great Ormond Street Institute of Child Health, Department of Developmental Biology and Cancer, Zayed Centre for Research into Rare Disease in Children, London, WC1N 1DZ, UK.ORCID http://orcid.org/0000-0001-9131-5849
Christy HungUCL Great Ormond Street Institute of Child Health, Department of Developmental Biology and Cancer, Zayed Centre for Research into Rare Disease in Children, London, WC1N 1DZ, UK.ORCID http://orcid.org/0000-0003-0056-7587
Tiana S BehrMRC Laboratory of Molecular Biology, Cambridge, CB2 0QH, UK.ORCID http://orcid.org/0000-0001-8832-8411
Bernardino GhettiDepartment of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Benjamin Ryskeldi-FalconMRC Laboratory of Molecular Biology, Cambridge, CB2 0QH, UK.
Emre KarakocOpen Targets, Wellcome Genome Campus, Cambridge, CB10 1SA, UK.
Francesco IorioOpen Targets, Wellcome Genome Campus, Cambridge, CB10 1SA, UK.ORCID http://orcid.org/0000-0001-7063-8913
Alastair ReithNovel Human Genetics Research Unit, GlaxoSmithKline Pharmaceuticals R&D, Stevenage, UK.ORCID http://orcid.org/0000-0001-5092-0604
Andrew R BassettOpen Targets, Wellcome Genome Campus, Cambridge, CB10 1SA, UK.ORCID http://orcid.org/0000-0003-1632-9137
Frederick J LiveseyUCL Great Ormond Street Institute of Child Health, Department of Developmental Biology and Cancer, Zayed Centre for Research into Rare Disease in Children, London, WC1N 1DZ, UK. rick@talisman-therapeutics.com.ORCID http://orcid.org/0000-0001-6128-3372

Funding

Alzheimer's Research UK (ARUK) Stem Cell Research CentreGreat Ormond Street Hospital Charity (GOSH) Stem Cell ProfessorshipNIHR | NIHR Great Ormond Street Hospital Biomedical Research Centre (BRC) N/AOpenTargets OTAR036Wellcome TrustWellcome Trust (WT) WT101052MA
6 · The paper itself

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.

Indexed as

Leucine-Rich Repeat Serine-Threonine Protein Kinase-2Low Density Lipoprotein Receptor-Related Protein-1Neuronstau ProteinsEndocytosisHumansInduced Pluripotent Stem CellsParkinson DiseaseTauopathiesLeucine-Rich Repeat Serine-Threonine Protein Kinase-2Low Density Lipoprotein Receptor-Related Protein-1LRP1 protein, humanLRRK2 protein, humanMAPT protein, humantau ProteinsAlzheimer’s DiseaseCRISPRFunctional GenomicsHuman iPSCsParkinson’s Disease

Identifiers

PMID40790356
PMCPMC12436637

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.