Evidence map›Paper›PMID 31456031›Full record

ArticleActa neuropathologica2019

Granulovacuolar degeneration bodies are neuron-selective lysosomal structures induced by intracellular tau pathology.

Vera I Wiersma, Anna Maria van Ziel, Sonia Vazquez-Sanchez, Anna Nölle, Ernesto Berenjeno-Correa, Anna Bonaterra-Pastra, Florence Clavaguera, Markus Tolnay, René J P Musters, Jan R T van Weering and 3 more

Open access · hybridAbstract read
In one paragraph

Article in Acta neuropathologica, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed, 1 pooled it
6.9field-weighted citation impact, top 2% of its field
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

54 citing papers in PubMed, 1 synthesis or guideline pooled it, 95 citations in OpenAlex.

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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

13 authors at 4 institutions in 4 countries.

Vera I WiersmaCenter for Neurogenomics and Cognitive Research, Department of Functional Genomics, Faculty of Science, Vrije Universiteit (VU), De Boelelaan 1085, 1081 HV, Amsterdam, The Netherlands.
Anna Maria van ZielCenter for Neurogenomics and Cognitive Research, Department of Functional Genomics, Faculty of Science, Vrije Universiteit (VU), De Boelelaan 1085, 1081 HV, Amsterdam, The Netherlands.
Sonia Vazquez-SanchezCenter for Neurogenomics and Cognitive Research, Department of Functional Genomics, Faculty of Science, Vrije Universiteit (VU), De Boelelaan 1085, 1081 HV, Amsterdam, The Netherlands.
Anna NölleDepartment of Pathology, Amsterdam University Medical Centers Location VUmc, Amsterdam, The Netherlands.
Ernesto Berenjeno-CorreaCenter for Neurogenomics and Cognitive Research, Department of Functional Genomics, Faculty of Science, Vrije Universiteit (VU), De Boelelaan 1085, 1081 HV, Amsterdam, The Netherlands.
Anna Bonaterra-PastraCenter for Neurogenomics and Cognitive Research, Department of Functional Genomics, Faculty of Science, Vrije Universiteit (VU), De Boelelaan 1085, 1081 HV, Amsterdam, The Netherlands.
Florence ClavagueraInstitut du Cerveau et de la Moelle épinière, INSERM U1127, CNRS UMR7225, Sorbonne Universités, Hôpital Pitié-Salpêtrière, Paris, France.
Markus TolnayInstitute of Medical Genetics and Pathology, University Hospital Basel, 4031, Basel, Switzerland.
René J P MustersDepartment of Physiology, Amsterdam University Medical Centers Location VUmc, Amsterdam, The Netherlands.
Jan R T van WeeringDepartment of Clinical Genetics, Amsterdam University Medical Centers Location VUmc, Amsterdam, The Netherlands.
Matthijs VerhageCenter for Neurogenomics and Cognitive Research, Department of Functional Genomics, Faculty of Science, Vrije Universiteit (VU), De Boelelaan 1085, 1081 HV, Amsterdam, The Netherlands.
Jeroen J M HoozemansDepartment of Pathology, Amsterdam University Medical Centers Location VUmc, Amsterdam, The Netherlands.
Wiep ScheperCenter for Neurogenomics and Cognitive Research, Department of Functional Genomics, Faculty of Science, Vrije Universiteit (VU), De Boelelaan 1085, 1081 HV, Amsterdam, The Netherlands. w.scheper@amsterdamumc.nl.ORCID 0000-0002-1431-4559
Amsterdam University Medical Centers · NLVrije Universiteit Amsterdam · NLCentre National de la Recherche Scientifique · FRUniversity Hospital of Basel · CH

Funding

Deltaplan Dementie 733050101
6 · The paper itself

Abstract

Granulovacuolar degeneration bodies (GVBs) are membrane-bound vacuolar structures harboring a dense core that accumulate in the brains of patients with neurodegenerative disorders, including Alzheimer's disease and other tauopathies. Insight into the origin of GVBs and their connection to tau pathology has been limited by the lack of suitable experimental models for GVB formation. Here, we used confocal, automated, super-resolution and electron microscopy to demonstrate that the seeding of tau pathology triggers the formation of GVBs in different mouse models in vivo and in primary mouse neurons in vitro. Seeding-induced intracellular tau aggregation, but not seed exposure alone, causes GVB formation in cultured neurons, but not in astrocytes. The extent of tau pathology strongly correlates with the GVB load. Tau-induced GVBs are immunoreactive for the established GVB markers CK1δ, CK1ɛ, CHMP2B, pPERK, peIF2α and pIRE1α and contain a LAMP1- and LIMP2-positive single membrane that surrounds the dense core and vacuole. The proteolysis reporter DQ-BSA is detected in the majority of GVBs, demonstrating that GVBs contain degraded endocytic cargo. GFP-tagged CK1δ accumulates in the GVB core, whereas GFP-tagged tau or GFP alone does not, indicating selective targeting of cytosolic proteins to GVBs. Taken together, we established the first in vitro model for GVB formation by seeding tau pathology in primary neurons. The tau-induced GVBs have the marker signature and morphological characteristics of GVBs in the human brain. We show that GVBs are lysosomal structures distinguished by the accumulation of a characteristic subset of proteins in a dense core.

Indexed as

AgedAged, 80 and overAnimalsAstrocytesBrainCells, CulturedDisease Models, AnimalDrugs, Chinese HerbalFemaleHumansLysosomesMaleMice, Inbred C57BLMice, TransgenicNeuronsTauopathiesDrugs, Chinese Herbalhuanshuaitau ProteinsCasein kinase 1 δGranulovacuolar degeneration bodiesLysosomeTau pathology

Identifiers

PMID31456031
PMCPMC6851499
OpenAlexW2971097757

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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 OpenQuestion graph.