Evidence map›Paper›PMID 36160042›Full record

ArticleCell reports methods2022

A next-generation iPSC-derived forebrain organoid model of tauopathy with tau fibrils by AAV-mediated gene transfer.

Hiroko Shimada, Yuta Sato, Takashi Sasaki, Aki Shimozawa, Kent Imaizumi, Tomoko Shindo, Sachiyo Miyao, Kosuke Kiyama, Takahiro Kondo, Shinsuke Shibata and 5 more

Abstract read
In one paragraph

Article in Cell reports methods, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 1 pooled it
–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

33 citing papers in PubMed, 1 synthesis or guideline pooled it.

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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

15 authors.

Hiroko ShimadaDepartment of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Yuta SatoGraduate School of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-8522, Japan.
Takashi SasakiCenter for Supercentenarian Medical Research, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Aki ShimozawaDepartment of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Kent ImaizumiDepartment of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Tomoko ShindoElectron Microscope Laboratory, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Sachiyo MiyaoDepartment of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Kosuke KiyamaDepartment of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Takahiro KondoDepartment of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Shinsuke ShibataDepartment of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Seiji IshiiDepartment of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Junro KuromitsuDepartment of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Hirofumi AoyagiDepartment of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Daisuke ItoDepartment of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Hideyuki OkanoDepartment of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

It is known that the human cellular models of Alzheimer's disease (AD) and tauopathy can only recapitulate the very early stage of the disease. To overcome these limitations, we developed a technology to make forebrain organoids (FBOs) from feeder-free induced pluripotent stem cells (iPSC)s by regulating a FGF2 concentration and applied this method to generate FBOs from patients with familial AD (fAD FBOs). The obtained fAD FBOs recapitulated the amyloid-β pathology and increased tau phosphorylation but not tau aggregates. To fully induce the tau pathology, FBOs were injected with adeno-associated virus (AAV)-expressing P301L mutant tau. In these Tau-P301L FBOs, tau fibrils were observed in the neuronal cell body and neurites with immunoelectron microscopy, in addition to the sarkosyl-insoluble and thioflavin S-positive phospho-tau aggregates. Collectively, this model can be used as a platform for investigating pathogenetic mechanisms and evaluation of target molecules for drug discovery for tauopathy.

Indexed as

Alzheimer DiseaseInduced Pluripotent Stem CellsTauopathiesDependovirusGene Transfer TechniquesHumansOrganoidsProsencephalontau Proteinstau ProteinsAAVAlzheimer's diseasebrain organoidsfeeder-free iPSCsFGF2tautauopathy

Identifiers

PMID36160042
PMCPMC9499998

What OpenQuestion holds

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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 OpenQuestion graph.