Evidence map›Paper›PMID 38659053›Full record

ArticleStem cell research & therapy2024

Simple modeling of familial Alzheimer's disease using human pluripotent stem cell-derived cerebral organoid technology.

Mu Seog Choe, Han Cheol Yeo, Joong Sun Kim, Jean Lee, Hae Jun Lee, Hyung-Ryong Kim, Kyung Min Baek, Na-Yeon Jung, Murim Choi, Min Young Lee

Open access · goldAbstract read
In one paragraph

Article in Stem cell research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 2 pooled it
5.8field-weighted citation impact, top 3% 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

21 citing papers in PubMed, 2 syntheses or guidelines pooled it, 25 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

10 authors at 7 institutions in 2 countries.

Mu Seog Choe *Department of Molecular Physiology, College of Pharmacy, Research Institute of Pharmaceutical Sciences, Vessel-Organ Interaction Research Center (VOICE, MRC), Kyungpook National University, 41566, Daegu, Republic of Korea.
Han Cheol Yeo *Department of Molecular Physiology, College of Pharmacy, Research Institute of Pharmaceutical Sciences, Vessel-Organ Interaction Research Center (VOICE, MRC), Kyungpook National University, 41566, Daegu, Republic of Korea.
Joong Sun Kim *Department of Veterinary Anatomy, College of Veterinary Medicine, Chonnam National University, 61186, Gwangju, Republic of Korea.
Jean LeeDepartment of Biochemistry and Biomedical Sciences, College of Medicine, Seoul National University, 03080, Seoul, Republic of Korea.
Hae Jun LeeDivision of Radiation Biomedical Research, Korea Institute of Radiological & Medical Sciences (KIRAMS), 01812, Seoul, Republic of Korea.
Hyung-Ryong KimDepartment of Pharmacology, College of Dentistry, Jeonbuk National University, 54896, Jeonju, Republic of Korea.
Kyung Min BaekDepartment of Cardiovascular and Neurologic Disease, College of Oriental Medicine, Daegu Haany University, 42158, Daegu, Republic of Korea.
Na-Yeon JungDepartment of Neurology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, 50612, Yangsan, Republic of Korea.
Murim ChoiDepartment of Biochemistry and Biomedical Sciences, College of Medicine, Seoul National University, 03080, Seoul, Republic of Korea. murimchoi@snu.ac.kr.
Min Young LeeDepartment of Molecular Physiology, College of Pharmacy, Research Institute of Pharmaceutical Sciences, Vessel-Organ Interaction Research Center (VOICE, MRC), Kyungpook National University, 41566, Daegu, Republic of Korea. vetmedic@knu.ac.kr.ORCID 0000-0003-0067-2803
Kyungpook National University · KRSeoul National University · KRChonnam National University · KRDaegu Haany University · KRJeonbuk National University · KRKorea Institute of Radiological and Medical Sciences · KRPusan National University Yangsan Hospital · KR

Funding

National Research Fund (KR) 2018R1D1A1A02044017National Research Fund (KR) 2020R1A5A2017323National Research Fund (KR) 2021R1F1A1047379National Research Fund (KR) 2023R1A2C2003446National Research Fund (KR) RS-2023-00223069National Research Fund (KR) RS-2023-00225239
6 · The paper itself

Abstract

backgroundCerebral organoids (COs) are the most advanced in vitro models that resemble the human brain. The use of COs as a model for Alzheimer's disease (AD), as well as other brain diseases, has recently gained attention. This study aimed to develop a human AD CO model using normal human pluripotent stem cells (hPSCs) that recapitulates the pathological phenotypes of AD and to determine the usefulness of this model for drug screening.

methodsWe established AD hPSC lines from normal hPSCs by introducing genes that harbor familial AD mutations, and the COs were generated using these hPSC lines. The pathological features of AD, including extensive amyloid-β (Aβ) accumulation, tauopathy, and neurodegeneration, were analyzed using enzyme-linked immunosorbent assay, Amylo-Glo staining, thioflavin-S staining, immunohistochemistry, Bielschowsky's staining, and western blot analysis.

resultsThe AD COs exhibited extensive Aβ accumulation. The levels of paired helical filament tau and neurofibrillary tangle-like silver deposits were highly increased in the AD COs. The number of cells immunoreactive for cleaved caspase-3 was significantly increased in the AD COs. In addition, treatment of AD COs with BACE1 inhibitor IV, a β-secretase inhibitor, and compound E, a γ-secretase inhibitor, significantly attenuated the AD pathological features.

conclusionOur model effectively recapitulates AD pathology. Hence, it is a valuable platform for understanding the mechanisms underlying AD pathogenesis and can be used to test the efficacy of anti-AD drugs.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesOrganoidsPluripotent Stem CellsAmyloid Precursor Protein SecretasesAspartic Acid EndopeptidasesBrainHumansModels, Biologicaltau ProteinsAmyloid beta-PeptidesAmyloid Precursor Protein SecretasesAspartic Acid EndopeptidasesBACE1 protein, humantau ProteinsAlzheimer’s diseaseCerebral organoidsDisease modelingDrug screeningHuman pluripotent stem cells

Identifiers

PMID38659053
PMCPMC11040922
OpenAlexW4395073943

What OpenQuestion holds

Textmetadata
LicenceCC BY
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 OpenQuestion graph.