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Human brain and organoid transcriptomes reveal key receptor tyrosine kinase pathways and genetic signatures in Alzheimer's disease.

Overview

Authors: Saewoon Shin1,2, Xiaohui Zhu1,2,3, Sarnai Amartumur1,2, Taehoon Lee2,4, Won Jong Yu2,5, Soomin Park1,2, Niloofar Etemadi1,2, Ariunzaya Jamsranjav1,2, Rian Kang2,4, Gyusoo Bak2,5, Dongjoon Lee6, Jieun Kim6, Jong Won Han6, Chaejeong Heo1,2, Hansang Cho1,2, Sunghoe Chang7,8, Inhee Mook-Jung6,9, Sang-Eun Lee10, Jong-Chan Park1,2,4,5
ORCID iDs: Sarnai Amartumur, Sunghoe Chang, Inhee Mook-Jung, Sang-Eun Lee
  1. Department of Biophysics, Sungkyunkwan University, Gyeonggi-do, Republic of Korea
  2. Institute of Quantum Biophysics, Sungkyunkwan University, Gyeonggi-do, Republic of Korea
  3. Graduate School of Stem Cell and Regenerative Biology, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea
  4. Department of Biopharmaceutical Convergence, Sungkyunkwan University, Suwon, Republic of Korea
  5. Department of Metabiohealth, Sungkyunkwan University, Gyeonggi-do, Republic of Korea
  6. Department of Biochemistry and Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Republic of Korea
  7. Department of Physiology and Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Republic of Korea
  8. Neuroscience Research Institute, Seoul National University Medical Research Center, Seoul, Republic of Korea
  9. Convergence Dementia Research Center, College of Medicine, Seoul National University, Seoul, Republic of Korea
  10. Department of Life Sciences, CHA University, Seongnam, Gyeonggi Republic of Korea
Institutions: Sungkyunkwan University (South Korea); Korea Advanced Institute of Science and Technology (South Korea); Seoul National University (South Korea); CHA University (South Korea)
Journal: Experimental & molecular medicine, volume 58, issue 4, pages 1230-1241
Dates: received 28 March 2025; accepted 13 January 2026; published online 15 April 2026; in print April 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s12276-026-01684-5 · PMID 41986478 · PMCID PMC13144494 · OpenAlex W7154478136
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: genetics / omics (modality), human (organism), Alzheimer's / dementia (population), cellular / molecular (subfield)
Methods: Machine learning, Statistics
Keywords: Alzheimer's disease, Molecular neuroscience
MeSH: Alzheimer Disease*, Brain*, Receptor Protein-Tyrosine Kinases*, Transcriptome*, Biomarkers, Gene Expression Profiling, Gene Expression Regulation, Gene Regulatory Networks, Humans, Protein Interaction Maps, Signal Transduction (* major topic)
Topic: Alzheimer's disease research and treatments (Physiology, Medicine), according to OpenAlex
Funding: Ministry of Health and Welfare (RS-2024-00339665); National Research Foundation of Korea (NRF-2022R1C1C2012736 and RS-2023-00266110, RS-2025-23323854)
Citations: not cited yet (Europe PMC); 39 references in the paper

Abstract

Alzheimer disease (AD) is a progressive neurodegenerative disorder marked by transcriptomic alterations affecting multiple genes. Many researchers have tried to predict major hallmarks of AD pathogenesis for diagnosis but the association between receptor tyrosine kinase (RTK) pathways and AD diagnosis is still unclear. This study aims to identify RTK-associated gene signatures crucial to AD pathogenesis and assess their potential as diagnostic biomarkers for AD. The study investigated changes in RTK pathway gene expression related to AD by analyzing brain transcriptome data from two independent public data sets (GSE84422 and GSE109887). Differentially expressed genes (DEGs) were analyzed from the GSE84422 and GSE109887 data sets and overlapping genes (oDEGs) were identified. RTK-related genes (ooDEGs) were subsequently selected through functional enrichment analysis. These were further refined into AD-related genes (disease-associated genes (DAGs)) through protein–protein interaction network analysis. Logistic regression and receiver operating characteristic analyses were conducted on the selected DAGs to evaluate their diagnostic potential, with additional gene expression validation performed in brain organoids and primary neurons. A total of 145 genes were identified as oDEGs in the above two data sets, and 18 genes were selected as ooDEGs. Six DAGs (ITGB1, AXL, GFAP, NRG1, CAV1, and RHOA) were selected. The diagnostic powers of the six DAGs for AD were 0.825 (GSE84422) and 0.884 (GSE109887). Human brain organoids and primary neuronal models were used to validate the biological relevance of these findings. AXL and ITGB1 were finally selected as key genes for RTK pathway in AD and were significantly increased in AD.

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Version 1, 29 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 19 authors, 2 keywords, 11 MeSH terms, 2 funders, 39 references.

Cite

This paper

Shin, S., Zhu, X., Amartumur, S., Lee, T., Yu, W. J., Park, S., Etemadi, N., Jamsranjav, A., Kang, R., Bak, G., Lee, D., Kim, J., Han, J. W., Heo, C., Cho, H., Chang, S., Mook-Jung, I., Lee, S.-E., & Park, J.-C. (2026). Human brain and organoid transcriptomes reveal key receptor tyrosine kinase pathways and genetic signatures in Alzheimer's disease. Experimental & molecular medicine, 58(4), 1230-1241. https://doi.org/10.1038/s12276-026-01684-5

BibTeX

@article{shin2026human,
author = {Shin, Saewoon and Zhu, Xiaohui and Amartumur, Sarnai and Lee, Taehoon and Yu, Won Jong and Park, Soomin and Etemadi, Niloofar and Jamsranjav, Ariunzaya and Kang, Rian and Bak, Gyusoo and Lee, Dongjoon and Kim, Jieun and Han, Jong Won and Heo, Chaejeong and Cho, Hansang and Chang, Sunghoe and Mook-Jung, Inhee and Lee, Sang-Eun and Park, Jong-Chan},
title = {{Human brain and organoid transcriptomes reveal key receptor tyrosine kinase pathways and genetic signatures in Alzheimer's disease}},
journal = {Experimental \& molecular medicine},
year = {2026},
month = apr,
volume = {58},
number = {4},
pages = {1230--1241},
publisher = {Korean Society for Biochemistry and Molecular Biology},
issn = {1226-3613},
doi = {10.1038/s12276-026-01684-5},
url = {https://doi.org/10.1038/s12276-026-01684-5},
pmid = {41986478},
pmcid = {PMC13144494}
}

RIS

TY - JOUR
AU - Shin, Saewoon
AU - Zhu, Xiaohui
AU - Amartumur, Sarnai
AU - Lee, Taehoon
AU - Yu, Won Jong
AU - Park, Soomin
AU - Etemadi, Niloofar
AU - Jamsranjav, Ariunzaya
AU - Kang, Rian
AU - Bak, Gyusoo
AU - Lee, Dongjoon
AU - Kim, Jieun
AU - Han, Jong Won
AU - Heo, Chaejeong
AU - Cho, Hansang
AU - Chang, Sunghoe
AU - Mook-Jung, Inhee
AU - Lee, Sang-Eun
AU - Park, Jong-Chan
TI - Human brain and organoid transcriptomes reveal key receptor tyrosine kinase pathways and genetic signatures in Alzheimer's disease
T2 - Experimental & molecular medicine
J2 - Exp Mol Med
PY - 2026
DA - 2026/04/15
VL - 58
IS - 4
SP - 1230
EP - 1241
SN - 1226-3613
PB - Korean Society for Biochemistry and Molecular Biology
DO - 10.1038/s12276-026-01684-5
UR - https://doi.org/10.1038/s12276-026-01684-5
LA - en
ER -

CSL-JSON

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