APOE4 Causes Widespread Molecular and Cellular Alterations Associated with Alzheimer’s Disease Phenotypes in Human iPSC-Derived Brain Cell Types

The Amyloid-β Pathway in Alzheimer’s Disease

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Apolipoprotein E and Alzheimer disease: pathobiology and targeting strategies

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Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease

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A single-cell atlas of entorhinal cortex from individuals with Alzheimer’s disease reveals cell-type-specific gene expression regulation

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A brief history of human disease genetics

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APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes

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Induced pluripotent stem cells (iPSCs): molecular mechanisms of induction and applications

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Cholesterol and matrisome pathways dysregulated in astrocytes and microglia

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Long-term maturation of human cortical organoids matches key early postnatal transitions

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Astrocyte Biomarkers in Alzheimer’s Disease

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ApoE Cascade Hypothesis in the pathogenesis of Alzheimer’s disease and related dementias

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Multi-lineage human iPSC-derived platforms for disease modeling and drug discovery

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Reconstruction of the human blood–brain barrier in vitro reveals a pathogenic mechanism of APOE4 in pericytes

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ApoE-Isoform-Dependent SARS-CoV-2 Neurotropism and Cellular Response

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Generation and biobanking of patient-derived glioblastoma organoids and their application in CAR T cell testing

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REST and neural gene network dysregulation in iPSC models of Alzheimer’s disease

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Assembling human brain organoids

Paşca, S. P. (2019) · Science · doi:10.1126/science.aau5729 · Cited by 208

Modeling Sporadic Alzheimer's Disease in Human Brain Organoids under Serum Exposure

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CRISPR-Cas Tools and Their Application in Genetic Engineering of Human Stem Cells and Organoids

Hendriks, D. F. G., Clevers, H. C., & Artegiani, B. (2020) · Cell stem cell · doi:10.1016/j.stem.2020.10.014 · Cited by 202

Microglia as Dynamic Cellular Mediators of Brain Function

Wright-Jin, E. C., & Gutmann, D. H. (2019) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2019.08.013 · Cited by 197

Lipopolysaccharide induces neuroinflammation in microglia by activating the MTOR pathway and downregulating Vps34 to inhibit autophagosome formation

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Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer’s disease

Najm, R., Jones, E. A., & Huang, Y. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0324-6 · Cited by 183

Depletion of the AD Risk Gene SORL1 Selectively Impairs Neuronal Endosomal Traffic Independent of Amyloidogenic APP Processing

Knupp, A., Mishra, S., Martinez, R., Braggin, J. E., Szabo, M., Kinoshita, C., Hailey, D. W., Small, S. A., Jayadev, S., & Young, J. E. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107719 · Cited by 165

Therapeutic approaches targeting Apolipoprotein E function in Alzheimer’s disease

Williams, T., Borchelt, D., & Chakrabarty, P. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-0358-9 · Cited by 172

Alzheimer's Disease Puzzle: Delving into Pathogenesis Hypotheses

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Brain cell type-specific cholesterol metabolism and implications for learning and memory

Li, D., Zhang, J., & Liu, Q. (2022) · Trends in Neurosciences · doi:10.1016/j.tins.2022.01.002 · Cited by 163

CRISPR-based functional genomics for neurological disease

Kampmann, M. (2020) · Nature Reviews Neurology · doi:10.1038/s41582-020-0373-z · Cited by 163

Amelioration of Tau and ApoE4-linked glial lipid accumulation and neurodegeneration with an LXR agonist

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Expression of the transcription factor PU.1 induces the generation of microglia-like cells in human cortical organoids

Cakir, B., Tanaka, Y., Kiral, F. R., Xiang, Y., Dagliyan, O., Wang, J., Lee, M., Greaney, A. M., Yang, W. S., duBoulay, C., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-28043-y · Cited by 162

Glial Contribution to Excitatory and Inhibitory Synapse Loss in Neurodegeneration

Henstridge, C. M., Tzioras, M., & Paolicelli, R. C. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00063 · Cited by 155

Neuronal apolipoprotein E4 increases cell death and phosphorylated tau release in alzheimer disease

Wadhwani, A. R., Affaneh, A., Van Gulden, S., & Kessler, J. A. (2019) · Annals of Neurology · doi:10.1002/ana.25455 · Cited by 142

Stem Cells, Genome Editing, and the Path to Translational Medicine

Soldner, F., & Jaenisch, R. (2018) · Cell · doi:10.1016/j.cell.2018.09.010 · Cited by 144

APOE-amyloid interaction: Therapeutic targets

Wisniewski, T., & Drummond, E. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104784 · Cited by 131

Three-dimensional modeling of human neurodegeneration: brain organoids coming of age

Grenier, K., Kao, J., & Diamandis, P. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0500-7 · Cited by 131

The APOE-R136S mutation protects against APOE4-driven tau pathology, neurodegeneration, and neuroinflammation

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Amyloid-β oligomers in cellular models of Alzheimer’s disease

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Comparative profiling of the synaptic proteome from Alzheimer’s disease patients with focus on the APOE genotype

Hesse, R., Hurtado, M. L., Jackson, R. J., Eaton, S. L., Herrmann, A. G., Colom-Cadena, M., Tzioras, M., King, D., Rose, J., Tulloch, J., et al. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0847-7 · Cited by 107

Moving beyond amyloid and tau to capture the biological heterogeneity of Alzheimer’s disease

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CNTN5-/+or EHMT2-/+human iPSC-derived neurons from individuals with autism develop hyperactive neuronal networks

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Cholesterol as a key player in amyloid β-mediated toxicity in Alzheimer’s disease

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ApoE4-dependent lysosomal cholesterol accumulation impairs mitochondrial homeostasis and oxidative phosphorylation in human astrocytes

Lee, H., Cho, S., Kim, M.-J., Park, Y. J., Cho, E., Jo, Y. S., Kim, Y.-S., Lee, J. Y., Thoudam, T., Woo, S.-H., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.113183 · Cited by 93

Down-syndrome-induced senescence disrupts the nuclear architecture of neural progenitors

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Advancing Drug Discovery for Neurological Disorders Using iPSC-Derived Neural Organoids

Costamagna, G., Comi, G. P., & Corti, S. P. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052659 · Cited by 91

Apolipoprotein E in Alzheimer’s disease: molecular insights and therapeutic opportunities

Belaidi, A. A., Bush, A. I., & Ayton, S. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00843-y · Cited by 91

Precision Nutrition for Alzheimer’s Prevention in ApoE4 Carriers

Norwitz, N. G., Saif, N., Ariza, I. E., & Isaacson, R. (2021) · Nutrients · doi:10.3390/nu13041362 · Cited by 92

Opposing effects of apoE2 and apoE4 on microglial activation and lipid metabolism in response to demyelination

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What are activated and reactive glia and what is their role in neurodegeneration?

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Application of CRISPR/Cas9 in Alzheimer’s Disease

Lu, L., Xi, Y., Cai, Y., Sun, M., & Yang, H. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.803894 · Cited by 79

Organoids to study immune functions, immunological diseases and immunotherapy

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Astrocytes and microglia in neurodegenerative diseases: Lessons from human in vitro models

Franklin, H., Clarke, B. E., & Patani, R. (2021) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2020.101973 · Cited by 66

Mitochondria-dependent phase separation of disease-relevant proteins drives pathological features of age-related macular degeneration

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The synthetic TRPML1 agonist ML-SA1 rescues Alzheimer-related alterations of the endosomal-autophagic-lysosomal system

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Cancer Chemotherapy Related Cognitive Impairment and the Impact of the Alzheimer’s Disease Risk Factor APOE

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A role of low-density lipoprotein receptor-related protein 4 (LRP4) in astrocytic Aβ clearance

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Amyloid-beta antibody binding to cerebral amyloid angiopathy fibrils and risk for amyloid-related imaging abnormalities

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Concise Review: Modeling Neurodegenerative Diseases with Human Pluripotent Stem Cell-Derived Microglia

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Cerebral organoids as tools to identify the developmental roots of autism

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APOE: The New Frontier in the Development of a Therapeutic Target towards Precision Medicine in Late-Onset Alzheimer’s

Yang, A., Kantor, B., & Chiba‐Falek, O. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22031244 · Cited by 51

Microglial Senescence and Activation in Healthy Aging and Alzheimer’s Disease: Systematic Review and Neuropathological Scoring

Malvaso, A., Gatti, A., Negro, G., Calatozzolo, C., Medici, V., & Poloni, T. E. (2023) · Cells · doi:10.3390/cells12242824 · Cited by 54

Phagocytosis of Apoptotic Cells Is Specifically Upregulated in ApoE4 Expressing Microglia in vitro

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Contribution of astrocytes to metabolic dysfunction in the Alzheimer’s disease brain

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From Brain Organoids to Networking Assembloids: Implications for Neuroendocrinology and Stress Medicine

Makrygianni, E. A., & Chrousos, G. P. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.621970 · Cited by 49

Optimization of cerebral organoids: a more qualified model for Alzheimer’s disease research

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Generation of pure monocultures of human microglia-like cells from induced pluripotent stem cells

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Microglial VPS35 deficiency impairs Aβ phagocytosis and Aβ-induced disease-associated microglia, and enhances Aβ associated pathology

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Cholesterol Dysmetabolism in Alzheimer’s Disease: A Starring Role for Astrocytes?

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LilrB3 is a putative cell surface receptor of APOE4

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Toxic amyloid-β oligomers induced self-replication in astrocytes triggering neuronal injury

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Mitochondrial dysfunction and oxidative stress in induced pluripotent stem cell models of Parkinson's disease

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Next Generation Precision Medicine: CRISPR-mediated Genome Editing for the Treatment of Neurodegenerative Disorders

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Invited Review – Understanding cause and effect in Alzheimer's pathophysiology: Implications for clinical trials

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Multi-functional role of apolipoprotein E in neurodegenerative diseases

Islam, S., Noorani, A. A., Sun, Y., Michikawa, M., & Zou, K. (2025) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2025.1535280 · Cited by 43

Critical Molecular and Cellular Contributors to Tau Pathology

Song, L., Wells, E. A., & Robinson, A. S. (2021) · Biomedicines · doi:10.3390/biomedicines9020190 · Cited by 40

The role of ApoE-mediated microglial lipid metabolism in brain aging and disease

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Simplified Brain Organoids for Rapid and Robust Modeling of Brain Disease

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Protein phosphatase 2A and complement component 4 are linked to the protective effect of APOE ɛ2 for Alzheimer's disease

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Modeling Alzheimer’s disease with human iPS cells: advancements, lessons, and applications

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ANKS1A regulates LDL receptor-related protein 1 (LRP1)-mediated cerebrovascular clearance in brain endothelial cells

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The application of in vitro ‐derived human neurons in neurodegenerative disease modeling

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Crosstalk between Different DNA Repair Pathways Contributes to Neurodegenerative Diseases

Gupta, S., You, P., SenGupta, T., Nilsen, H. L., & Sharma, K. (2021) · Biology · doi:10.3390/biology10020163 · Cited by 37

APOE2 mitigates disease-related phenotypes in an isogenic hiPSC-based model of Alzheimer’s disease

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PDE inhibition in distinct cell types to reclaim the balance of synaptic plasticity

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A small-molecule TLR4 antagonist reduced neuroinflammation in female E4FAD mice

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Challenges and Future Perspectives in Modeling Neurodegenerative Diseases Using Organ‐on‐a‐Chip Technology

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Advanced in vitro models: Microglia in action

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Astrocytic response mediated by the CLU risk allele inhibits OPC proliferation and myelination in a human iPSC model

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Astrocytes: From the Physiology to the Disease

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Microglia and its Genetics in Alzheimer's Disease

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Current understanding of the interactions between metal ions and Apolipoprotein E in Alzheimer’s disease

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Glutamine Antagonist JHU-083 Normalizes Aberrant Hippocampal Glutaminase Activity and Improves Cognition in APOE4 Mice

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Photoaffinity Labeling and Quantitative Chemical Proteomics Identify LXRβ as the Functional Target of Enhancers of Astrocytic apoE

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Prevention of Alzheimer's disease through diet: An exploratory review

Bhuiyan, N. Z., Hasan, M. K., Mahmud, Z., Hossain, M. S., & Rahman, A. (2023) · Metabolism Open · doi:10.1016/j.metop.2023.100257 · Cited by 35

Implication of tau propagation on neurodegeneration in Alzheimer’s disease

Lamontagne-Kam, D., Ulfat, A. K., Hervé, V., Vu, T.-M., & Brouillette, J. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1219299 · Cited by 28

Back to the origins: Human brain organoids to investigate neurodegeneration

Faravelli, I., Costamagna, G., Tamanini, S., & Corti, S. (2020) · Brain Research · doi:10.1016/j.brainres.2019.146561 · Cited by 25

A combined physiologically‐based pharmacokinetic and quantitative systems pharmacology model for modeling amyloid aggregation in Alzheimer's disease

Geerts, H., Walker, M., Rose, R., Bergeler, S., van der Graaf, P. H., Schuck, E. L., Koyama, A., Yasuda, S., Hussein, Z., Reyderman, L., et al. (2023) · CPT Pharmacometrics & Systems Pharmacology · doi:10.1002/psp4.12912 · Cited by 24

Comprehensive Bibliometric Analysis of Stem Cell Research in Alzheimer’s Disease from 2004 to 2022

Wang, R., Zhu, Y., Qin, L.-F., Xu, Z., Gao, X.-R., Liu, C., Xu, G., & Chen, Y. (2023) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000528886 · Cited by 24

Latest advances in mechanisms of epileptic activity in Alzheimer’s disease and dementia with Lewy Bodies

Vicente, M. C., Addo-Osafo, K., & Vossel, K. A. (2024) · Frontiers in Neurology · doi:10.3389/fneur.2024.1277613 · Cited by 25

Human iPSC-derived microglial cells protect neurons from neurodegeneration in long-term cultured adhesion brain organoids

Chen, X., Sun, G., Feng, L., Tian, E., & Shi, Y. (2025) · Communications Biology · doi:10.1038/s42003-024-07401-0 · Cited by 23

Inflammation-induced lysosomal dysfunction in human iPSC-derived microglia is exacerbated by APOE 4/4 genotype

Hellén, M., Weert, I., Müller, S. A., Räsänen, N., Kettunen, P., Lehtonen, Š., Peitz, M., Fließbach, K., Takalo, M., Koskuvi, M., et al. (2025) · Journal of Neuroinflammation · doi:10.1186/s12974-025-03470-y · Cited by 25

iPSC-derived blood-brain barrier modeling reveals APOE isoform-dependent interactions with amyloid beta

Ding, Y., Palecek, S. P., & Shusta, E. V. (2024) · Fluids and Barriers of the CNS · doi:10.1186/s12987-024-00580-2 · Cited by 22

APOE4 transforms the transcriptome

Ridler, C. E. (2018) · Nature Reviews Neurology · doi:10.1038/s41582-018-0034-7 · Cited by 1

Differential effects of apolipoprotein E on the molecular and cellular phenotypes associated with Alzheimer’s disease in isogenic human iPSC‐derived neurons

You, Y., Poon, W. W., Jun, G., Farrer, L. A., & Ikezu, T. (2020) · Alzheimer s & Dementia · doi:10.1002/alz.044579

Trading places

Lewis, S. (2018) · Nature reviews. Neuroscience · doi:10.1038/s41583-018-0032-1

Modelling AD‐relevant pathophysiology in neurons, astrocytes and microglia from two complete sets of isogenic iPSC lines generated by the ADAPTED project

Socorro, A. C., Schmid, B., Clausen, C., Holst, B., Peitz, M., Grezella, C., Brüstle, O., Bahnassawy, L., Bennett, K. L., Ried, J. S., et al. (2020) · Alzheimer s & Dementia · doi:10.1002/alz.040278

P4‐263: NEURONAL APOE MODULATES A SPORADIC ALZHEIMER'S DISEASE PHENOTYPE IN PATIENT‐DERIVED INDUCED NEURONS

Wadhwani, A. R., & Kessler, J. A. (2018) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2018.07.085