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APOE4 Causes Widespread Molecular and Cellular Alterations Associated with Alzheimer’s Disease Phenotypes in Human iPSC-Derived Brain Cell Types
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“Our well-powered hiPSC study identified common and divergent pathways when compared to earlier APOE4 hiPSC studies (Lin et al., 2018; Sienski et al., 2021; Wang et al., 2018).”
From Cholesterol and matrisome pathways dysregulated in astrocytes and microglia (2022) · cites this paper as Lin et al., 2018
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Additionally, upregulation of synaptogenesis suggests a compensatory effect in APOE4 mice as previous work has found the APOE4 allele is associated with altered synaptic density [39][40][41] .”
From APOE4-drives brain bioenergetic shifts independent of Alzheimer’s disease pathology (2026) · cites this paper as [41]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Using technical replicates from one isogenic pair, Lin et al. reported intracellular free cholesterol accumulation in APOE4 astrocytes, consistent with our data, but identified downregulated cholesterol biosynthesis, opposing our data.”
From Cholesterol and matrisome pathways dysregulated in astrocytes and microglia (2022) · cites this paper as Lin et al., 2018
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“in which adding microglia (Abreu et al., 2018; Lin et al., 2018) to such models with increasing cellular complexity may further mimic the brain environment.”
From Cholesterol and matrisome pathways dysregulated in astrocytes and microglia (2022) · cites this paper as Lin et al., 2018
Experimental — accuracy not yet measuredIn the citing paper
“Compared to isogenic APOE3, APOE4 variants featured an increased number of synapses and elevated Aβ42 secretion in neurons, while APOE4 astrocytes showed impaired Aβ uptake and cholesterol accumulation [465].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [465]
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Items 201–215 of 215
Wang, N., Wang, M., Jeevaratnam, S., Rosenberg, C. L., Ikezu, T. C., Shue, F., Doss, S. V., Alnobani, A., Martens, Y. A., Wren, M. C., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21622310
Wang, N., Wang, M., Jeevaratnam, S., Rosenberg, C. L., Ikezu, T. C., Shue, F., Doss, S. V., Alnobani, A., Martens, Y. A., Wren, M. C., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21622298
Wang, N., Wang, M., Jeevaratnam, S., Rosenberg, C. L., Ikezu, T. C., Shue, F., Doss, S. V., Alnobani, A., Martens, Y. A., Wren, M. C., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21622295
APOE Gene Editing as a Therapeutic Target Toward Precision Medicine in AD
Teter, B., Campagna, J. J., Spilman, P. R., & John, V. (2025) · Springer eBooks · doi:10.1007/978-3-031-52641-1_73-1 · Cited by 1
Chen, H., Zhang, H., Yang, M., Xie, Q., & Zhu, L. (2026) · Journal of Alzheimer s Disease · doi:10.1177/13872877261416064 · Cited by 1
Advances in modeling memory decline: A critical overview of current animal and human paradigms
Peng, Y., Li, Y., Ma, L., Wu, T., & Chen, G. (2026) · Ageing Research Reviews · doi:10.1016/j.arr.2026.103172
APOE Gene Editing as a Therapeutic Target Toward Precision Medicine in AD
Teter, B., Campagna, J. J., Spilman, P., & John, V. (2026) · Springer eBooks · doi:10.1007/978-3-031-96089-5_73
APOE4 and INPP5D converge on membrane mechanics to regulate endocytosis in human astrocytesPreprint
Gevorgyan, A. S., Gordon, L. M., Combs, C. A., Lita, A., Yang, L. G., Cuní‐López, C., Root, J. T., Larion, M., Taraska, J. W., & Narayan, P. S. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.22.726347
Increased CSF PKR activation in Alzheimer’s disease is associated with APOE4 genotype
Duquesne, L., Vrillon, A., Martinet, M., Nisemblat, Y., Paquet, C., Hugon, J., & Mouton‐Liger, F. (2026) · Alzheimer s Research & Therapy · doi:10.1186/s13195-026-02203-4
Nikolova, M. T., Freitag, K., Okamoto, R., Catellani, A., Hinke, J., Luginbühl, N., Lin, H., Kaindl, J., He, Z., Wahle, P., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.09.25.754357
Dynamic contributions of astrocytes in Alzheimer’s disease
Guo, F., Li, T., & He, X. (2026) · Experimental Neurology · doi:10.1016/j.expneurol.2026.116032
From Amyloid Exposure to Genetic Causality: Converging hiPSC-Based Models of Alzheimer’s Disease
Colasuonno, F., Valenza, A., Rossin, F., & Moreno, S. (2026) · Cells · doi:10.3390/cells15191793
Shi, C. H., Zhu, B., Pina-Crespo, J., Chen, W. N., Vo, G. V., Huang, H., Yip, K. Y., & Huang, T. Y. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.10.15.759523
Zhang, H., Xiang, L., Zhang, L., Zhai, X., Yan, Y., Zhou, X., Zhang, Y., Yao, S., & Xia, Y. (2026) · International Conference on Biomedical and Intelligent Systems (IC-BIS) · doi:10.1145/3841905.3841960
Metadata
- Authors
- Lin, Y.-T., Seo, J., Gao, F., Feldman, H. M., Wen, H.-L., Penney, J., Cam, H. P., Gjoneska, E., Raja, W. K., Cheng, J., Rueda, R., Kritskiy, O., Abdurrob, F., Peng, Z., Milo, B., Yu, C. J., Elmsaouri, S., Dey, D., Ko, T., Yankner, B. A., & Tsai, L.-H.
- Corresponding author
- Tsai, Li-Huei
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2018-06
- Volume
- 98
- Issue
- 6
- Pages
- 1294
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W4247032901
- Cited by
- 210
- References
- 0
- Citations by year
- 2026: 18 · 2025: 24 · 2024: 22 · 2023: 27 · 2022: 27 · 2021: 27 · 2020: 34 · 2019: 27 · 2018: 4
- FWCI
- 15.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- Funders
- National Institute on Aging (RC1AG036106, RF1-AG048029, RF1AG048056)
- National Institute of Mental Health (R01MH113279)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- APOE ε4, Alzheimer's disease, APOE3, induced pluripotent stem cells, iPSC-derived neurons, astrocytes, microglia, organoids, gene expression changes, synaptic transmission, miniature excitatory postsynaptic currents, isogenic cell lines
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