ApoE expression across the CNS: Who, What, Where, When, and How (much)?

Nolt, Georgia L.; Lucido, Chloe C.; Smith, Lily M.; Johnson, Lance A.

doi:10.1186/s44477-026-00028-x

Cited by 2Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsBarrier Structure and Function Studies

ApoE expression across the CNS: Who, What, Where, When, and How (much)?

Open access

Nolt, Georgia L., Lucido, Chloe C., Smith, Lily M., Johnson, Lance A.·2026·Molecular Neurodegeneration Advances

DOI 10.1186/s44477-026-00028-xPMC PMC13216210

Open this paper in CoChat — free account

Abstract

Apolipoprotein E ( APOE ) is the strongest genetic risk factor for late-onset Alzheimer’s disease (AD) and encodes a major lipid transporter in the central nervous system (CNS). Although apoE has been studied extensively, fundamental questions remain regarding its expression across the CNS. For example, which CNS cell types express APOE ? Where is APOE expression enriched across brain regions? When is APOE dynamically regulated – across development, aging, injury, and neurodegeneration? How much apoE is produced at the mRNA and protein level – particularly across the common E2, E3, and E4 isoforms? Here, we synthesize transcriptomic, spatial, biochemical, and genetic evidence to provide an organized framework for the “who, what, where, when, and how (much)” of CNS APOE /apoE. By assessing large-scale single-cell datasets along with in vivo and cell-type–specific genetic studies, we highlight that astrocytes are the predominant source of CNS apoE at baseline, while microglia, oligodendrocyte-lineage cells, vascular-associated populations, and border-interface macrophages exhibit context-dependent induction that is strongly influenced by aging, injury, and AD-related pathology. We also evaluate unresolved discrepancies, such as the extent of neuronal APOE expression and its contribution to total brain apoE, and describe how – across modalities – apoE abundance often follows an isoform-dependent hierarchy (typically E2 > E3 > E4 at the protein level) while transcript–protein discordance and model-specific effects underscore substantial post-transcriptional and contextual regulation. Finally, we discuss how clarifying spatiotemporal, cell-specific, and isoform-dependent apoE expression will enable better informed and more precise apoE-targeted therapeutic strategies.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1186/s44477-026-00028-x

Cites

209 of 209 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Gene Dose of Apolipoprotein E Type 4 Allele and the Risk of Alzheimer's Disease in Late Onset Families
Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., Roses, A. D., Haines, J. L., & Pericak-Vance, M. A. (1993) · Science · doi:10.1126/science.8346443 · Cited by 9,429 · see citing works
A Unique Microglia Type Associated with Restricting Development of Alzheimer’s Disease
Keren-Shaul, H., Spinrad, A., Weiner, A., Matcovitch-Natan, O., Dvir-Szternfeld, R., Ulland, T. K., David, E., Baruch, K., Lara-Astaiso, D., Toth, B., et al. (2017) · Cell · doi:10.1016/j.cell.2017.05.018 · Cited by 5,493 · cited 4× · see citing works
“In fact, APOE is a core gene that drives the disease associated microglia (DAM) phenotype observed in AD ( discussed further in the “When” section ) [39, 77, 78].”
Influential
An RNA-Sequencing Transcriptome and Splicing Database of Glia, Neurons, and Vascular Cells of the Cerebral Cortex
Zhang, Y., Chen, K., Sloan, S. A., Bennett, M. L., Scholze, A. R., O'Keeffe, S., Phatnani, H. P., Guarnieri, P., Caneda, C., Ruderisch, N., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.1860-14.2014 · Cited by 4,875 · cited 1× · see citing works
“Numerous in vivo studies converge on the estimate that 75%–80% of apoE in the brain can be attributed to astrocytic production [12, 26, 28, 29, 31–35].”
Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease.
Strittmatter, W. J., Saunders, A. M., Schmechel, D., Pericak-Vance, M., Enghild, J., Salvesen, G. S., & Roses, A. D. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.5.1977 · Cited by 4,268 · see citing works
Association of apolipoprotein E allele ϵ4 with late‐onset familial and sporadic Alzheimer's disease
Saunders, A. M., Strittmatter, W. J., Schmechel, D., St. George-Hyslop, P. H., Pericak-Vance, M. A., Joo, S. H., Rosi, B. L., Gusella, J. F., Crapper-MacLachlan, D. R., Alberts, M. J., et al. (1993) · Neurology · doi:10.1212/wnl.43.8.1467 · Cited by 3,786 · see citing works
The TREM2-APOE Pathway Drives the Transcriptional Phenotype of Dysfunctional Microglia in Neurodegenerative Diseases
Krasemann, S., Madore, C., Cialic, R., Baufeld, C., Calcagno, N., El Fatimy, R., Beckers, L., O’Loughlin, E., Xu, Y., Fanek, Z., et al. (2017) · Immunity · doi:10.1016/j.immuni.2017.08.008 · Cited by 2,979 · see citing works
Single-cell transcriptomic analysis of Alzheimer’s disease
Mathys, H., Davila-Velderrain, J., Peng, Z., Gao, F., Mohammadi, S., Young, J. Z., Menon, M., He, L., Abdurrob, F., Jiang, X., et al. (2019) · Nature · doi:10.1038/s41586-019-1195-2 · Cited by 2,568 · see citing works
Purification and Characterization of Progenitor and Mature Human Astrocytes Reveals Transcriptional and Functional Differences with Mouse
Zhang, Y., Sloan, S. A., Clarke, L. E., Caneda, C., Plaza, C. A., Blumenthal, P. D., Vogel, H., Steinberg, G. K., Edwards, M. S. B., Li, G., et al. (2016) · Neuron · doi:10.1016/j.neuron.2015.11.013 · Cited by 2,295 · see citing works
Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease
Corder, E. H., Saunders, A. M., Risch, N. J., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Rimmler, J. B., Locke, P. A., Conneally, P. M., Schmader, K. E., et al. (1994) · Nature Genetics · doi:10.1038/ng0694-180 · Cited by 1,920 · see citing works
A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain
Yao, Z., van Velthoven, C. T. J., Kunst, M., Zhang, M., McMillen, D., Lee, C., Jung, W., Goldy, J., Abdelhak, A., Aitken, M., et al. (2023) · Nature · doi:10.1038/s41586-023-06812-z · Cited by 1,194 · cited 6× · see citing works
“2a-b) [36–38] .”
Influential
A single-cell atlas of mouse brain macrophages reveals unique transcriptional identities shaped by ontogeny and tissue environment
Van Hove, H., Martens, L., Scheyltjens, I., De Vlaminck, K., Pombo Antunes, A. R., De Prijck, S., Vandamme, N., De Schepper, S., Van Isterdael, G., Scott, C. L., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0393-4 · Cited by 1,160 · see citing works
Disease-associated astrocytes in Alzheimer’s disease and aging
Habib, N., McCabe, C., Medina, S., Varshavsky, M., Kitsberg, D., Dvir-Szternfeld, R., Green, G., Dionne, D., Nguyen, L., Marshall, J. L., et al. (2020) · Nature Neuroscience · doi:10.1038/s41593-020-0624-8 · Cited by 1,009 · see citing works
A single-cell atlas of entorhinal cortex from individuals with Alzheimer’s disease reveals cell-type-specific gene expression regulation
Grubman, A., Chew, G., Ouyang, J. F., Sun, G., Choo, X. Y., McLean, C., Simmons, R. K., Buckberry, S., Vargas-Landin, D. B., Poppe, D., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0539-4 · Cited by 956 · see citing works
Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer’s Disease
Chen, W.-T., Lu, A., Craessaerts, K., Pavie, B., Sala Frigerio, C., Corthout, N., Qian, X., Laláková, J., Kühnemund, M., Voytyuk, I., et al. (2020) · Cell · doi:10.1016/j.cell.2020.06.038 · Cited by 949 · cited 1× · see citing works
“…studies report apoE-isoform-dependent alterations in oligodendrocyte populations and function in AD and related neurodegenerative diseases, defining how oligo-dendrocyte apoE/ APOE is regulated across cell states, insults, and apoE isoforms remains an important gap in the field [94, 98, 101–105].”
Transcriptomic diversity of cell types across the adult human brain
Siletti, K., Hodge, R., Mossi Albiach, A., Lee, K. W., Ding, S.-L., Hu, L., Lönnerberg, P., Bakken, T., Casper, T., Clark, M., et al. (2023) · Science · doi:10.1126/science.add7046 · Cited by 832 · see citing works
Apolipoprotein E: Structure and function in lipid metabolism, neurobiology, and Alzheimer’s diseases
Huang, Y., & Mahley, R. W. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.08.025 · Cited by 829 · see citing works
Apolipoprotein E associated with astrocytic glia of the central nervous system and with nonmyelinating glia of the peripheral nervous system.
Boyles, J. K., Pitas, R. E., Wilson, E., Mahley, R. W., & Taylor, J. M. (1985) · Journal of Clinical Investigation · doi:10.1172/jci112130 · Cited by 829 · see citing works
A human brain vascular atlas reveals diverse mediators of Alzheimer’s risk
Yang, A. C., Vest, R. T., Kern, F., Lee, D. P., Agam, M., Maat, C. A., Losada, P. M., Chen, M. B., Schaum, N., Khoury, N., et al. (2022) · Nature · doi:10.1038/s41586-021-04369-3 · Cited by 797 · see citing works
Apolipoprotein E and Apolipoprotein E Receptors: Normal Biology and Roles in Alzheimer Disease
Holtzman, D. M., Herz, J., & Bu, G. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006312 · Cited by 782 · see citing works
Astrocytes synthesize apolipoprotein E and metabolize apolipoprotein E-containing lipoproteins
Pitas, R. E., Boyles, J. K., Lee, S. H., Foss, D., & Mahley, R. W. (1987) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(87)90295-5 · Cited by 693 · see citing works
Resistance to autosomal dominant Alzheimer’s disease in an APOE3 Christchurch homozygote: a case report
Arboleda-Velasquez, J. F., Lopera, F., O’Hare, M., Delgado-Tirado, S., Marino, C., Chmielewska, N., Saez-Torres, K. L., Amarnani, D., Schultz, A. P., Sperling, R. A., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0611-3 · Cited by 598 · see citing works
Defective cholesterol clearance limits remyelination in the aged central nervous system
Cantuti-Castelvetri, L., Fitzner, D., Bosch-Queralt, M., Weil, M.-T., Su, M., Sen, P., Ruhwedel, T., Mitkovski, M., Trendelenburg, G., Lütjohann, D., et al. (2018) · Science · doi:10.1126/science.aan4183 · Cited by 586 · see citing works
Loss of TREM2 function increases amyloid seeding but reduces plaque-associated ApoE
Parhizkar, S., Arzberger, T., Brendel, M., Kleinberger, G., Deussing, M., Focke, C., Nuscher, B., Xiong, M., Ghasemigharagoz, A., Katzmarski, N., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-018-0296-9 · Cited by 555 · see citing works
APOE4/4 is linked to damaging lipid droplets in Alzheimer’s disease microglia
Haney, M. S., Pálovics, R., Munson, C. N., Long, C., Johansson, P. K., Yip, O., Dong, W., Rawat, E., West, E., Schlachetzki, J. C. M., et al. (2024) · Nature · doi:10.1038/s41586-024-07185-7 · Cited by 536 · cited 1× · see citing works
“These isoform-specific differences - particularly the reduced phagocytic capacity and diminished lipid-efflux capacity associated with E4 - contribute to increased lipid droplet accumulation and impaired clearance of amyloid-β and cellular debris relative to E3 or E2 [83, 94, 205].”
Profile and Regulation of Apolipoprotein E (ApoE) Expression in the CNS in Mice with Targeting of Green Fluorescent Protein Gene to the ApoE Locus
Xu, Q., Bernardo, A., Walker, D., Kanegawa, T., Mahley, R. W., & Huang, Y. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.5476-05.2006 · Cited by 524 · see citing works
APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes
Blanchard, J. W., Akay, L. A., Davila-Velderrain, J., von Maydell, D., Mathys, H., Davidson, S. M., Effenberger, A., Chen, C.-Y., Maner-Smith, K., Hajjar, I., et al. (2022) · Nature · doi:10.1038/s41586-022-05439-w · Cited by 493 · cited 4× · see citing works
“Isoform-specific patterns of apoE within oligodendrocytes remain underexplored, although available data suggests that E3 and E4 oligodendrocytes express comparable apoE levels that decline with aging regardless of genotype [39, 101].”
Influential
Astrocyte layers in the mammalian cerebral cortex revealed by a single-cell in situ transcriptomic map
Bayraktar, O. A., Bartels, T., Holmqvist, S., Kleshchevnikov, V., Martirosyan, A., Polioudakis, D., Ben Haim, L., Young, A. M. H., Batiuk, M. Y., Prakash, K., et al. (2020) · Nature Neuroscience · doi:10.1038/s41593-020-0602-1 · Cited by 489 · see citing works
White matter aging drives microglial diversity
Safaiyan, S., Besson-Girard, S., Kaya, T., Cantuti-Castelvetri, L., Liu, L., Ji, H., Schifferer, M., Gouna, G., Usifo, F., Kannaiyan, N., et al. (2021) · Neuron · doi:10.1016/j.neuron.2021.01.027 · Cited by 477 · see citing works
Exceptionally low likelihood of Alzheimer’s dementia in APOE2 homozygotes from a 5,000-person neuropathological study
Reiman, E. M., Arboleda-Velasquez, J. F., Quiroz, Y. T., Huentelman, M. J., Beach, T. G., Caselli, R. J., Chen, Y., Su, Y., Myers, A. J., Hardy, J., et al. (2020) · Nature Communications · doi:10.1038/s41467-019-14279-8 · Cited by 473 · see citing works
Age-Specific Epigenetic Drift in Late-Onset Alzheimer's Disease
Wang, S.-C., Oelze, B., & Schumacher, A. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002698 · Cited by 467 · see citing works
ApoE4 Accelerates Early Seeding of Amyloid Pathology
Liu, C.-C., Zhao, N., Fu, Y., Wang, N., Linares, C., Tsai, C.-W., & Bu, G. (2017) · Neuron · doi:10.1016/j.neuron.2017.11.013 · Cited by 451 · see citing works
ApoE4: an emerging therapeutic target for Alzheimer’s disease
Safieh, M., Korczyn, A. D., & Michaelson, D. M. (2019) · BMC Medicine · doi:10.1186/s12916-019-1299-4 · Cited by 449 · see citing works
Microglia drive APOE-dependent neurodegeneration in a tauopathy mouse model
Shi, Y., Manis, M., Long, J., Wang, K., Sullivan, P. M., Remolina Serrano, J., Hoyle, R., & Holtzman, D. M. (2019) · Journal of Experimental Medicine · doi:10.1084/jem.20190980 · Cited by 448 · see citing works
Gain of toxic apolipoprotein E4 effects in human iPSC-derived neurons is ameliorated by a small-molecule structure corrector
Wang, C., Najm, R., Xu, Q., Jeong, D.-E., Walker, D., Balestra, M. E., Yoon, S. Y., Yuan, H., Li, G., Miller, Z. A., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0004-z · Cited by 428 · see citing works
Alzheimer’s Patient Microglia Exhibit Enhanced Aging and Unique Transcriptional Activation
Srinivasan, K., Friedman, B. A., Etxeberria, A., Huntley, M. A., van der Brug, M. P., Foreman, O., Paw, J. S., Modrusan, Z., Beach, T. G., Serrano, G. E., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107843 · Cited by 427 · see citing works
Cholesterol and matrisome pathways dysregulated in astrocytes and microglia
TCW, J., Qian, L., Pipalia, N. H., Chao, M. J., Liang, S. A., Shi, Y., Jain, B. R., Bertelsen, S. E., Kapoor, M., Marcora, E., et al. (2022) · Cell · doi:10.1016/j.cell.2022.05.017 · Cited by 411 · see citing works
ApoE4 Impairs Neuron-Astrocyte Coupling of Fatty Acid Metabolism
Qi, G., Mi, Y., Shi, X., Gu, H., Brinton, R. D., & Yin, F. (2021) · Cell Reports · doi:10.1016/j.celrep.2020.108572 · Cited by 379 · see citing works
Impact of Apolipoprotein E (ApoE) Polymorphism on Brain ApoE Levels
Riddell, D. R., Zhou, H., Atchison, K., Warwick, H. K., Atkinson, P. J., Jefferson, J., Xu, L., Aschmies, S., Kirksey, Y., Hu, Y., et al. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.1972-08.2008 · Cited by 342 · see citing works
Selective removal of astrocytic APOE4 strongly protects against tau-mediated neurodegeneration and decreases synaptic phagocytosis by microglia
Wang, C., Xiong, M., Gratuze, M., Bao, X., Shi, Y., Andhey, P. S., Manis, M., Schroeder, C., Yin, Z., Madore, C., et al. (2021) · Neuron · doi:10.1016/j.neuron.2021.03.024 · Cited by 334 · see citing works
Genotyping and sequence analysis of apolipoprotein E isoforms*1
EMI, M. (1988) · Genomics · doi:10.1016/0888-7543(88)90130-9 · Cited by 301 · see citing works
Apolipoprotein E: Structural Insights and Links to Alzheimer Disease Pathogenesis
Chen, Y., Strickland, M. R., Soranno, A., & Holtzman, D. M. (2021) · Neuron · doi:10.1016/j.neuron.2020.10.008 · Cited by 298 · see citing works
GABAergic Interneuron Dysfunction Impairs Hippocampal Neurogenesis in Adult Apolipoprotein E4 Knockin Mice
Li, G., Bien-Ly, N., Andrews-Zwilling, Y., Xu, Q., Bernardo, A., Ring, K., Halabisky, B., Deng, C., Mahley, R. W., & Huang, Y. (2009) · Cell Stem Cell · doi:10.1016/j.stem.2009.10.015 · Cited by 288 · see citing works
Apolipoprotein E in lipid metabolism and neurodegenerative disease
Yang, L. G., March, Z. M., Stephenson, R. A., & Narayan, P. S. (2023) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2023.05.002 · Cited by 286 · see citing works
Reconstruction of the human blood–brain barrier in vitro reveals a pathogenic mechanism of APOE4 in pericytes
Blanchard, J. W., Bula, M., Davila-Velderrain, J., Akay, L. A., Zhu, L., Frank, A., Victor, M. B., Bonner, J. M., Mathys, H., Lin, Y.-T., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0886-4 · Cited by 283 · see citing works
Blood-brain barrier-associated pericytes internalize and clear aggregated amyloid-β42 by LRP1-dependent apolipoprotein E isoform-specific mechanism
Ma, Q., Zhao, Z., Sagare, A. P., Wu, Y., Wang, M., Owens, N. C., Verghese, P. B., Herz, J., Holtzman, D. M., & Zlokovic, B. V. (2018) · Molecular Neurodegeneration · doi:10.1186/s13024-018-0286-0 · Cited by 281 · see citing works
APOE in the bullseye of neurodegenerative diseases: impact of the APOE genotype in Alzheimer’s disease pathology and brain diseases
Fernández-Calle, R., Konings, S. C., Frontiñán-Rubio, J., García-Revilla, J., Camprubí-Ferrer, L., Svensson, M., Martinson, I., Boza-Serrano, A., Venero, J. L., Nielsen, H. M., et al. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00566-4 · Cited by 278 · see citing works
Glymphatic distribution of CSF-derived apoE into brain is isoform specific and suppressed during sleep deprivation
Achariyar, T. M., Li, B., Peng, W., Verghese, P. B., Shi, Y., McConnell, E., Benraiss, A., Kasper, T., Song, W., Takano, T., et al. (2016) · Molecular Neurodegeneration · doi:10.1186/s13024-016-0138-8 · Cited by 250 · see citing works
A shared disease-associated oligodendrocyte signature among multiple CNS pathologies
Kenigsbuch, M., Bost, P., Halevi, S., Chang, Y., Chen, S., Ma, Q., Hajbi, R., Schwikowski, B., Bodenmiller, B., Fu, H., et al. (2022) · Nature Neuroscience · doi:10.1038/s41593-022-01104-7 · Cited by 233 · see citing works
LRP1 in Brain Vascular Smooth Muscle Cells Mediates Local Clearance of Alzheimer's Amyloid-β
Kanekiyo, T., Liu, C., Shinohara, M., Li, J., & Bu, G. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.3987-12.2012 · Cited by 221 · see citing works
APOE ε4/ε4 diminishes neurotrophic function of human iPSC-derived astrocytes
Zhao, J., Davis, M. D., Martens, Y. A., Shinohara, M., Graff-Radford, N. R., Younkin, S. G., Wszolek, Z. K., Kanekiyo, T., & Bu, G. (2017) · Human Molecular Genetics · doi:10.1093/hmg/ddx155 · Cited by 221 · see citing works
Association of apolipoprotein E genotype with brain levels of apolipoprotein E and apolipoprotein J (clusterin) in Alzheimer disease
Bertrand, P., Poirier, J., Oda, T., Finch, C. E., & Pasinetti, G. M. (1995) · Molecular Brain Research · doi:10.1016/0169-328x(95)00097-c · Cited by 210 · see citing works
APOE4 Causes Widespread Molecular and Cellular Alterations Associated with Alzheimer’s Disease Phenotypes in Human iPSC-Derived Brain Cell Types
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., et al. (2018) · Neuron · doi:10.1016/j.neuron.2018.06.011 · Cited by 210 · see citing works
Age-Dependent Effects of apoE Reduction Using Antisense Oligonucleotides in a Model of β-amyloidosis
Huynh, T.-P. V., Liao, F., Francis, C. M., Robinson, G. O., Serrano, J. R., Jiang, H., Roh, J., Finn, M. B., Sullivan, P. M., Esparza, T. J., et al. (2017) · Neuron · doi:10.1016/j.neuron.2017.11.014 · Cited by 209 · see citing works
Gene delivery of human apolipoprotein E alters brain Aβ burden in a mouse model of Alzheimer's disease
Dodart, J.-C., Marr, R. A., Koistinaho, M., Gregersen, B. M., Malkani, S., Verma, I. M., & Paul, S. M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409072102 · Cited by 207 · see citing works
Cerebrospinal fluid APOE levels: an endophenotype for genetic studies for Alzheimer's disease
Cruchaga, C., Kauwe, J. S. K., Nowotny, P., Bales, K., Pickering, E. H., Mayo, K., Bertelsen, S., Hinrichs, A., Fagan, A. M., Holtzman, D. M., et al. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds296 · Cited by 207 · see citing works
The Choroid Plexus and Cerebrospinal Fluid: Emerging Roles in Development, Disease, and Therapy
Lehtinen, M. K., Bjornsson, C. S., Dymecki, S. M., Gilbertson, R. J., Holtzman, D. M., & Monuki, E. S. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.3258-13.2013 · Cited by 204 · see citing works
APOE modulates microglial immunometabolism in response to age, amyloid pathology, and inflammatory challenge
Lee, S., Devanney, N. A., Golden, L. R., Smith, C. T., Schwartz, J. L., Walsh, A. E., Clarke, H. A., Goulding, D. S., Allenger, E. J., Morillo-Segovia, G., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112196 · Cited by 203 · see citing works
Self-citation
APOE4 impairs the microglial response in Alzheimer’s disease by inducing TGFβ-mediated checkpoints
Yin, Z., Rosenzweig, N., Kleemann, K. L., Zhang, X., Brandão, W., Margeta, M. A., Schroeder, C., Sivanathan, K. N., Silveira, S., Gauthier, C., et al. (2023) · Nature Immunology · doi:10.1038/s41590-023-01627-6 · Cited by 202 · cited 3× · see citing works
“For example, in P301S mice, microglial APOE expression is more than two-fold higher in E4 than in E3 mice, whereas no isoform difference is detected in APP/PS1 mice, highlighting pathology-specific expression patterns [82].”
Cell type‐specific roles of APOE4 in Alzheimer disease
Blumenfeld, J., Yip, O., Kim, M. J., & Huang, Y. (2024) · Nature Reviews Neuroscience · doi:10.1038/s41583-023-00776-9 · Cited by 202 · see citing works
Multifaceted roles of APOE in Alzheimer disease
Jackson, R. J., Hyman, B. T., & Serrano-Pozo, A. (2024) · Nature Reviews Neurology · doi:10.1038/s41582-024-00988-2 · Cited by 193 · see citing works
ApoE Lipidation as a therapeutic target in Alzheimer’s disease
Lanfranco, M. F., Ng, C. A., & Rebeck, G. W. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176336 · Cited by 189 · see citing works
Neuronal ApoE upregulates MHC-I expression to drive selective neurodegeneration in Alzheimer’s disease
Zalocusky, K. A., Najm, R., Taubes, A. L., Hao, Y., Yoon, S. Y., Koutsodendris, N., Nelson, M. R., Rao, A., Bennett, D. A., Bant, J., et al. (2021) · Nature Neuroscience · doi:10.1038/s41593-021-00851-3 · Cited by 189 · see citing works
Lipid Metabolism Crosstalk in the Brain: Glia and Neurons
Barber, C. N., & Raben, D. M. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00212 · Cited by 188 · see citing works
Gene Transfer of Human Apoe Isoforms Results in Differential Modulation of Amyloid Deposition and Neurotoxicity in Mouse Brain
Hudry, E., Dashkoff, J., Roe, A. D., Takeda, S., Koffie, R. M., Hashimoto, T., Scheel, M., Spires-Jones, T., Arbel-Ornath, M., Betensky, R., et al. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3007000 · Cited by 187 · see citing works
Alzheimer's Disease Genetic Risk Factor APOE-ε4 Also Affects Normal Brain Function
Battista, A. M. D., Heinsinger, N. M., & Rebeck, G. W. (2016) · Current Alzheimer Research · doi:10.2174/1567205013666160401115127 · Cited by 184 · see citing works
Specific Regional Transcription of Apolipoprotein E in Human Brain Neurons
Xu, P., Gilbert, J. R., Qiu, H.-L., Ervin, J. F., Rothrock‐Christian, T., Hulette, C., & Schmechel, D. E. (1999) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)65305-9 · Cited by 177 · see citing works
AAVrh.10-Mediated APOE2 Central Nervous System Gene Therapy for APOE4-Associated Alzheimer's Disease
Rosenberg, J. B., Kaplitt, M. G., De, B. P., Chen, A., Flagiello, T., Salami, C., Pey, E., Zhao, L., Ricart Arbona, R. J., Monette, S., et al. (2018) · Human Gene Therapy Clinical Development · doi:10.1089/humc.2017.231 · Cited by 169 · see citing works
Total apolipoprotein E levels and specific isoform composition in cerebrospinal fluid and plasma from Alzheimer’s disease patients and controls
Martínez-Morillo, E., Hansson, O., Atagi, Y., Bu, G., Minthon, L., Diamandis, E. P., & Nielsen, H. M. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1266-2 · Cited by 168 · see citing works
Apolipoprotein E4 Alters Astrocyte Fatty Acid Metabolism and Lipid Droplet Formation
Farmer, B., Kluemper, J., & Johnson, L. (2019) · Cells · doi:10.3390/cells8020182 · Cited by 164 · see citing works
Self-citation
Expression and secretion of <scp>apoE</scp> isoforms in astrocytes and microglia during inflammation
Lanfranco, M. F., Sepulveda, J., Kopetsky, G., & Rebeck, G. W. (2021) · Glia · doi:10.1002/glia.23974 · Cited by 164 · see citing works
Opposing effects of viral mediated brain expression of apolipoprotein E2 (apoE2) and apoE4 on apoE lipidation and Aβ metabolism in apoE4-targeted replacement mice
Hu, J., Liu, C.-C., Chen, X.-F., Zhang, Y.-W., Xu, H., & Bu, G. (2015) · Molecular Neurodegeneration · doi:10.1186/s13024-015-0001-3 · Cited by 161 · see citing works
Apolipoprotein E2-Christchurch (136 Arg----Ser). New variant of human apolipoprotein E in a patient with type III hyperlipoproteinemia.
Wardell, M. R., Brennan, S. O., Janus, E. D., Fraser, R., & Carrell, R. W. (1987) · Journal of Clinical Investigation · doi:10.1172/jci113096 · Cited by 159 · see citing works
Multiomic spatial landscape of innate immune cells at human central nervous system borders
Sankowski, R., Süß, P., Benkendorff, A., Böttcher, C., Fernandez-Zapata, C., Chhatbar, C., Cahueau, J., Monaco, G., Gasull, A. D., Khavaran, A., et al. (2024) · Nature Medicine · doi:10.1038/s41591-023-02673-1 · Cited by 156 · see citing works
APOE in the normal brain
Flowers, S. A., & Rebeck, G. W. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.104724 · Cited by 149 · see citing works
Beyond the CNS: The many peripheral roles of APOE
Martínez-Martínez, A. B., Torres-Perez, E., Devanney, N., Del Moral, R., Johnson, L. A., & Arbones-Mainar, J. M. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104809 · Cited by 149 · see citing works
Self-citation
Cell-autonomous effects of APOE4 in restricting microglial response in brain homeostasis and Alzheimer’s disease
Liu, C.-C., Wang, N., Chen, Y., Inoue, Y., Shue, F., Ren, Y., Wang, M., Qiao, W., Ikezu, T. C., Li, Z., et al. (2023) · Nature Immunology · doi:10.1038/s41590-023-01640-9 · Cited by 146 · see citing works
APOE ε2 is associated with increased tau pathology in primary tauopathy
Zhao, N., Liu, C.-C., Van Ingelgom, A. J., Linares, C., Kurti, A., Knight, J. A., Heckman, M. G., Diehl, N. N., Shinohara, M., Martens, Y. A., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-06783-0 · Cited by 139 · see citing works
Lack of hepatic apoE does not influence early Aβ deposition: observations from a new APOE knock-in model
Huynh, T.-P. V., Wang, C., Tran, A. C., Tabor, G. T., Mahan, T. E., Francis, C. M., Finn, M. B., Spellman, R., Manis, M., Tanzi, R. E., et al. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0337-1 · Cited by 139 · see citing works
Astroglial Regulation of Apolipoprotein E Expression in Neuronal Cells
Harris, F. M., Tesseur, I., Brecht, W. J., Xu, Q., Mullendorff, K., Chang, S., Wyss-Coray, T., Mahley, R. W., & Huang, Y. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m309475200 · Cited by 135 · see citing works
Overexpressing low‐density lipoprotein receptor reduces tau‐associated neurodegeneration in relation to apoE‐linked mechanisms
Shi, Y., Andhey, P. S., Ising, C., Wang, K., Snipes, L. L., Boyer, K., Lawson, S., Yamada, K., Qin, W., Manis, M., et al. (2021) · Neuron · doi:10.1016/j.neuron.2021.05.034 · Cited by 135 · see citing works
Selective reduction of astrocyte apoE3 and apoE4 strongly reduces Aβ accumulation and plaque-related pathology in a mouse model of amyloidosis
Mahan, T. E., Wang, C., Bao, X., Choudhury, A., Ulrich, J. D., & Holtzman, D. M. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00516-0 · Cited by 134 · see citing works
Quantitative proteomics of acutely-isolated mouse microglia identifies novel immune Alzheimer’s disease-related proteins
Rangaraju, S., Dammer, E. B., Raza, S. A., Gao, T., Xiao, H., Betarbet, R. S., Duong, D. M., Webster, J. A., Hales, C. M., Lah, J. J., et al. (2018) · Molecular Neurodegeneration · doi:10.1186/s13024-018-0266-4 · Cited by 133 · see citing works
Small-Molecule Structure Correctors Target Abnormal Protein Structure and Function: Structure Corrector Rescue of Apolipoprotein E4–Associated Neuropathology: Miniperspective
Mahley, R. W., & Huang, Y. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm3008618 · Cited by 132 · see citing works
Neuronal APOE4 removal protects against tau-mediated gliosis, neurodegeneration and myelin deficits
Koutsodendris, N., Blumenfeld, J., Agrawal, A., Traglia, M., Grone, B., Zilberter, M., Yip, O., Rao, A., Nelson, M. R., Hao, Y., et al. (2023) · Nature Aging · doi:10.1038/s43587-023-00368-3 · Cited by 132 · see citing works
Oligodendroglial fatty acid metabolism as a central nervous system energy reserve
Asadollahi, E., Trevisiol, A., Saab, A. S., Looser, Z. J., Dibaj, P., Ebrahimi, R., Kusch, K., Ruhwedel, T., Möbius, W., Jahn, O., et al. (2024) · Nature Neuroscience · doi:10.1038/s41593-024-01749-6 · Cited by 130 · see citing works
Anti-ApoE Antibody Given after Plaque Onset Decreases Aβ Accumulation and Improves Brain Function in a Mouse Model of Aβ Amyloidosis
Liao, F., Hori, Y., Hudry, E., Bauer, A. Q., Jiang, H., Mahan, T. E., Lefton, K. B., Zhang, T. J., Dearborn, J. T., Kim, J., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.0646-14.2014 · Cited by 128 · cited 1× · see citing works
“…through antibodies, antisense oligonucleotides, or RNA interference, and supplementing E2 expression via gene therapy have all demonstrated promising potential to reverse aspects of E4-driven pathology (amyloid burden, metabolic shifts, reductions in gliosis) [171, 189–191, 203, 204, 209–213].”
In vivo measurement of apolipoprotein E from the brain interstitial fluid using microdialysis
Ulrich, J. D., Burchett, J. M., Restivo, J. L., Schuler, D. R., Verghese, P. B., Mahan, T. E., Landreth, G. E., Castellano, J. M., Jiang, H., Cirrito, J. R., et al. (2013) · Molecular Neurodegeneration · doi:10.1186/1750-1326-8-13 · Cited by 128 · see citing works
Cell-specific production, secretion, and function of apolipoprotein E
Kockx, M., Traini, M., & Kritharides, L. (2018) · Journal of Molecular Medicine · doi:10.1007/s00109-018-1632-y · Cited by 124 · see citing works
25-Hydroxycholesterol amplifies microglial IL-1β production in an apoE isoform-dependent manner
Wong, M. Y., Lewis, M., Doherty, J. J., Shi, Y., Cashikar, A. G., Amelianchik, A., Tymchuk, S., Sullivan, P. M., Qian, M., Covey, D. F., et al. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01869-3 · Cited by 121 · see citing works
Soluble apoE/Aβ complex: mechanism and therapeutic target for APOE4-induced AD risk
Tai, L. M., Mehra, S., Shete, V., Estus, S., Rebeck, G. W., Bu, G., & LaDu, M. J. (2014) · Molecular Neurodegeneration · doi:10.1186/1750-1326-9-2 · Cited by 116 · see citing works
Genetic Restoration of Plasma ApoE Improves Cognition and Partially Restores Synaptic Defects in ApoE-Deficient Mice
Lane-Donovan, C., Wong, W. M., Durakoglugil, M. S., Wasser, C. R., Jiang, S., Xian, X., & Herz, J. (2016) · The Journal of Neuroscience · doi:10.1523/jneurosci.1054-16.2016 · Cited by 115 · see citing works
Marked regional differences of brain human apolipoprotein e expression in targeted replacement mice
Sullivan, P. M., Mace, B. E., Maeda, N., & Schmechel, D. E. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2003.10.011 · Cited by 113 · see citing works
Reduced levels of human apoE4 protein in an animal model of cognitive impairment
Sullivan, P. M., Han, B., Liu, F., Mace, B. E., Ervin, J. F., Wu, S., Koger, D., Paul, S., & Bales, K. R. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2009.05.011 · Cited by 113 · see citing works
Microglial efferocytosis: Diving into the Alzheimer’s disease gene pool
Romero-Molina, C., Garretti, F., Andrews, S. J., Marcora, E., & Goate, A. M. (2022) · Neuron · doi:10.1016/j.neuron.2022.10.015 · Cited by 111 · cited 2× · see citing works
“Beyond its role in lipid transport, apoE also functions as an opsonin that facilitates microglial phagocytosis of apoptotic cells and other substrates, with apoE isoforms showing distinct efficiencies in this process [95].”
Apolipoprotein E Expression by Neurons Surviving Excitotoxic Stress
Boschert, U., Merlo‐Pich, E., Higgins, G. A., Roses, A. D., & Catsicas, S. (1999) · Neurobiology of Disease · doi:10.1006/nbdi.1999.0251 · Cited by 110 · see citing works
ApoE is required for maintenance of the dentate gyrus neural progenitor pool
Yang, C.-P., Gilley, J. A., Zhang, G., & Kernie, S. G. (2011) · Development · doi:10.1242/dev.065540 · Cited by 109 · see citing works
APOE3 -Jacksonville (V236E) variant reduces self-aggregation and risk of dementia
Liu, C.-C., Murray, M. E., Li, X., Zhao, N., Wang, N., Heckman, M. G., Shue, F., Martens, Y., Li, Y., Raulin, A.-C., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abc9375 · Cited by 108 · see citing works
Intracerebral adeno-associated virus gene delivery of apolipoprotein E2 markedly reduces brain amyloid pathology in Alzheimer's disease mouse models
Zhao, L., Gottesdiener, A. J., Parmar, M., Li, M., Kaminsky, S. M., Chiuchiolo, M. J., Sondhi, D., Sullivan, P. M., Holtzman, D. M., Crystal, R. G., et al. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.04.020 · Cited by 107 · see citing works
Border-associated macrophages in the central nervous system
Sun, R., & Jiang, H. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03059-x · Cited by 107 · see citing works
The cell biology of APOE in the brain
Windham, I. A., & Cohen, S. (2024) · Trends in Cell Biology · doi:10.1016/j.tcb.2023.09.004 · Cited by 103 · see citing works
Apolipoprotein E4 produced in GABAergic interneurons causes learning and memory deficits in mice
Knoferle, J., Yoon, S. Y., Walker, D., Leung, L., Gillespie, A. K., Tong, L. M., Bien-Ly, N., & Huang, Y. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.2281-14.2014 · Cited by 97 · see citing works
Glial-neuron crosstalk in health and disease: A focus on metabolism, obesity, and cognitive impairment
Henn, R. E., Noureldein, M. H., Elzinga, S. E., Kim, B., Savelieff, M. G., & Feldman, E. L. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105766 · Cited by 97 · see citing works
APOE traffics to astrocyte lipid droplets and modulates triglyceride saturation and droplet size
Windham, I. A., Powers, A. E., Ragusa, J. V., Wallace, E. D., Zanellati, M. C., Williams, V. H., Wagner, C. H., White, K. K., & Cohen, S. (2024) · Journal of Cell Biology · doi:10.1083/jcb.202305003 · Cited by 96 · see citing works
The role of APOE4 in Alzheimer’s disease: strategies for future therapeutic interventions
Hunsberger, H. C., Pinky, P. D., Smith, W., Suppiramaniam, V., & Reed, M. N. (2019) · Neuronal Signaling · doi:10.1042/ns20180203 · Cited by 94 · see citing works
Association of Rare APOE Missense Variants V236E and R251G With Risk of Alzheimer Disease
Le Guen, Y., Belloy, M. E., Grenier-Boley, B., de Rojas, I., Castillo-Morales, A., Jansen, I., Nicolas, A., Bellenguez, C., Dalmasso, C., Küçükali, F., et al. (2022) · JAMA Neurology · doi:10.1001/jamaneurol.2022.1166 · Cited by 93 · see citing works
Measurement of Apolipoprotein E (apoE) in Cerebrospinal Fluid
Hesse, C., Larsson, H. E., Fredman, P., Minthon, L., Andreasen, N., Davidsson, P., & Blennow, K. (2000) · Neurochemical Research · doi:10.1023/a:1007516210548 · Cited by 89 · see citing works
ApoE (Apolipoprotein E) in brain pericytes regulates endothelial function in an isoform-dependent manner by modulating basement membrane components
Yamazaki, Y., Shinohara, M., Yamazaki, A., Ren, Y., Asmann, Y. W., Kanekiyo, T., & Bu, G. (2020) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.119.313169 · Cited by 89 · see citing works
APOE2 gene therapy reduces amyloid deposition and improves markers of neuroinflammation and neurodegeneration in a mouse model of Alzheimer disease
Jackson, R. J., Keiser, M. S., Meltzer, J. C., Fykstra, D. P., Dierksmeier, S. E., Hajizadeh, S., Kreuzer, J., Morris, R., Melloni, A., Nakajima, T., et al. (2024) · Molecular Therapy · doi:10.1016/j.ymthe.2024.03.024 · Cited by 86 · see citing works
Transcriptomic atlas and interaction networks of brain cells in mouse CNS demyelination and remyelination
Hou, J., Zhou, Y., Cai, Z., Terekhova, M., Swain, A., Andhey, P. S., Guimaraes, R. M., Ulezko Antonova, A., Qiu, T., Sviben, S., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112293 · Cited by 85 · see citing works
Apolipoprotein E levels in cerebrospinal fluid and the effects of ABCA1polymorphisms
Wahrle, S. E., Shah, A. R., Fagan, A. M., Smemo, S., Kauwe, J. S., Grupe, A., Hinrichs, A., Mayo, K., Jiang, H., Thal, L. J., et al. (2007) · Molecular Neurodegeneration · doi:10.1186/1750-1326-2-7 · Cited by 84 · see citing works
Brain region‐specific amyloid plaque‐associated myelin lipid loss, APOE deposition and disruption of the myelin sheath in familial Alzheimer’s disease mice
Kaya, I., Jennische, E., Lange, S., Baykal, A. T., Malmberg, P., & Fletcher, J. S. (2020) · Journal of Neurochemistry · doi:10.1111/jnc.14999 · Cited by 84 · see citing works
Opposing effects of apoE2 and apoE4 on microglial activation and lipid metabolism in response to demyelination
Wang, N., Wang, M., Jeevaratnam, S., Rosenberg, C., Ikezu, T. C., Shue, F., Doss, S. V., Alnobani, A., Martens, Y. A., Wren, M., et al. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00577-1 · Cited by 82 · see citing works
Border-associated macrophages as gatekeepers of brain homeostasis and immunity
Vara‐Pérez, M., & Movahedi, K. (2025) · Immunity · doi:10.1016/j.immuni.2025.04.005 · Cited by 81 · see citing works
Regulation of Oligodendrocyte Functions: Targeting Lipid Metabolism and Extracellular Matrix for Myelin Repair
Marangon, D., Boccazzi, M., Lecca, D., & Fumagalli, M. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9020470 · Cited by 77 · see citing works
Regulation of astrocyte lipid metabolism and ApoE secretion by the microglial oxysterol, 25-hydroxycholesterol
Cashikar, A. G., Toral-Rios, D., Timm, D., Romero, J., Strickland, M., Long, J. M., Han, X., Holtzman, D. M., & Paul, S. M. (2023) · Journal of Lipid Research · doi:10.1016/j.jlr.2023.100350 · Cited by 72 · see citing works
CSF Apo-E levels associate with cognitive decline and MRI changes
Initiative, F. T. A. D. N., Toledo, J. B., Da, X., Weiner, M. W., Wolk, D. A., Xie, S. X., Arnold, S. E., Davatzikos, C., Shaw, L. M., & Trojanowski, J. Q. (2014) · Acta Neuropathologica · doi:10.1007/s00401-013-1236-0 · Cited by 71 · see citing works
Apolipoprotein E lipoprotein particles inhibit amyloid-β uptake through cell surface heparan sulphate proteoglycan
Fu, Y., Zhao, J., Atagi, Y., Nielsen, H. M., Liu, C., Zheng, H., Shinohara, M., Kanekiyo, T., & Bu, G. (2016) · Molecular Neurodegeneration · doi:10.1186/s13024-016-0099-y · Cited by 71 · see citing works
Vascular ApoE4 impairs behavior by modulating gliovascular function
Yamazaki, Y., Liu, C.-C., Yamazaki, A., Shue, F., Martens, Y. A., Chen, Y., Qiao, W., Kurti, A., Oue, H., Ren, Y., et al. (2021) · Neuron · doi:10.1016/j.neuron.2020.11.019 · Cited by 71 · see citing works
Increased neuronal damage and apoE immunoreactivity in human apolipoprotein E, E4 isoform-specific, transgenic mice after global cerebral ischaemia
Horsburgh, K. J., McCulloch, J., Nilsen, M., Roses, A. D., & Nicoll, J. A. R. (2000) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2000.01339.x · Cited by 70 · see citing works
ApoE Regulates the Development of Adult Newborn Hippocampal Neurons
Tensaouti, Y., Stephanz, E. P., Yu, T., & Kernie, S. G. (2018) · eNeuro · doi:10.1523/eneuro.0155-18.2018 · Cited by 67 · see citing works
Reducing microglial lipid load enhances β amyloid phagocytosis in an Alzheimer’s disease mouse model
Wu, X., Miller, J. A., Lee, B. T. K., Wang, Y., & Ruedl, C. (2025) · Science Advances · doi:10.1126/sciadv.adq6038 · Cited by 67 · see citing works
From Genetics to Neuroinflammation: The Impact of ApoE4 on Microglial Function in Alzheimer’s Disease
Dias, D., Portugal, C. C., Relvas, J. B., & Socodato, R. (2025) · Cells · doi:10.3390/cells14040243 · Cited by 66 · see citing works
A cell-autonomous role for border-associated macrophages in ApoE4 neurovascular dysfunction and susceptibility to white matter injury
Anfray, A., Schaeffer, S. M., Hattori, Y., Santisteban, M. M., Casey, N., Wang, G., Strickland, M. R., Zhou, P., Holtzman, D. M., Anrather, J., et al. (2024) · Nature Neuroscience · doi:10.1038/s41593-024-01757-6 · Cited by 64 · see citing works
APOE mRNA and protein expression in postmortem brain are modulated by an extended haplotype structure
Bekris, L. M., Galloway, N. M., Montine, T. J., Schellenberg, G. D., & Yu, C. (2009) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30993 · Cited by 63 · see citing works
Apolipoprotein E Inhibits Cerebrovascular Pericyte Mobility through a RhoA Protein-mediated Pathway
Casey, C. S., Atagi, Y., Yamazaki, Y., Shinohara, M., Tachibana, M., Fu, Y., Bu, G., & Kanekiyo, T. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.625251 · Cited by 62 · see citing works
Oligodendrocyte precursor cells: the multitaskers in the brain
Fang, L., & Bai, X. (2023) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-023-02837-5 · Cited by 62 · see citing works
ApoE4 reduction: An emerging and promising therapeutic strategy for Alzheimer's disease
Li, Y., Macyczko, J. R., Liu, C.-C., & Bu, G. (2022) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2022.03.011 · Cited by 61 · see citing works
Transcriptional landscape of human microglia implicates age, sex, and APOE‐related immunometabolic pathway perturbations
Patel, T., Carnwath, T., Wang, X., Allen, M., Lincoln, S., Lewis‐Tuffin, L. J., Quicksall, Z., Lin, S., Tutor‐New, F. Q., Ho, C. C. G., et al. (2022) · Aging Cell · doi:10.1111/acel.13606 · Cited by 60 · see citing works
White matter microstructure is altered in cognitively normal middle-aged APOE-ε4 homozygotes
Study, F. T. A., Operto, G., Cacciaglia, R., Grau‐Rivera, O., Falcón, C., Brugulat‐Serrat, A., Ródenas, P., Ramos, R., Morán, S., Esteller, M., et al. (2018) · Alzheimer s Research & Therapy · doi:10.1186/s13195-018-0375-x · Cited by 59 · see citing works
Apolipoprotein E protects cultured pericytes and astrocytes from D-Aβ1–40-mediated cell death
Bruinsma, I. B., Wilhelmus, M. M. M., Kox, M., Veerhuis, R., de Waal, R. M. W., & Verbeek, M. M. (2009) · Brain Research · doi:10.1016/j.brainres.2009.12.039 · Cited by 58 · see citing works
ABCA1/ApoE/HDL Signaling Pathway Facilitates Myelination and Oligodendrogenesis after Stroke
Li, L., Li, R., Zacharek, A., Wang, F., Landschoot‐Ward, J., Chopp, M., Chen, J., & Cui, X. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21124369 · Cited by 57 · see citing works
Choroid Plexus Acts as Gatekeeper for TREM2, Abnormal Accumulation of ApoE, and Fibrillary Tau in Alzheimer’s Disease and in Down Syndrome Dementia
Raha‐Chowdhury, R., Henderson, J. W., Raha, A. A., Vuono, R., Bickerton, A., Jones, E. A., Fincham, R., Allinson, K. S. J., Holland, A. J., & Zaman, S. H. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-181179 · Cited by 56 · see citing works
Apolipoprotein E Genotype Regulates Amyloid-β Cytotoxicity
Wilhelmus, M. M. M., Otte‐Höller, I., Davis, J., Nostrand, W. E. V., de Waal, R. M. W., & Verbeek, M. M. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.4213-04.2005 · Cited by 54 · see citing works
Peripheral Versus Central Nervous System APOE in Alzheimer’s Disease: Interplay across the Blood-Brain Barrier
Chernick, D., Ortiz-Valle, S., Jeong, A., Qu, W., & Li, L. (2019) · Neuroscience Letters · doi:10.1016/j.neulet.2019.134306 · Cited by 54 · see citing works
Developmental profiling of postnatal dentate gyrus progenitors provides evidence for dynamic cell‐autonomous regulation
Gilley, J. A., Yang, C., & Kernie, S. G. (2009) · Hippocampus · doi:10.1002/hipo.20719 · Cited by 53 · see citing works
Decreased Cerebrospinal Fluid Apolipoprotein E After Subarachnoid Hemorrhage
Kay, A., Petzold, A., Kerr, M., Keir, G., Thompson, E. J., & Nicoll, J. A. R. (2003) · Stroke · doi:10.1161/01.str.0000057579.25430.16 · Cited by 52 · see citing works
The multifaceted roles of apolipoprotein E4 in Alzheimer’s disease pathology and potential therapeutic strategies
Chen, Y., Jin, H., Chen, J., Li, J., Găman, M., & Zou, Z. (2025) · Cell Death Discovery · doi:10.1038/s41420-025-02600-y · Cited by 52 · see citing works
Introducing Human APOE into Aβ Transgenic Mouse Models
Tai, L. M., Youmans, K. L., Jungbauer, L., Yu, C., & LaDu, M. J. (2011) · International Journal of Alzheimer’s Disease · doi:10.4061/2011/810981 · Cited by 52 · see citing works
Regionally specific neuronal expression of human APOE gene in transgenic mice
Xu, P., Gilbert, J. R., Qiu, H.-L., Rothrock‐Christian, T., Settles, D. L., Roses, A. D., & Schmechel, D. E. (1998) · Neuroscience Letters · doi:10.1016/s0304-3940(98)00247-x · Cited by 50 · see citing works
An atlas of the aging mouse proteome reveals the features of age-related post-transcriptional dysregulation
Takasugi, M., Nonaka, Y., Takemura, K., Yoshida, Y., Stein, F., Schwarz, J., Adachi, J., Satoh, J., Ito, S., Tombline, G., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-52845-x · Cited by 50 · see citing works
Relevance of the quantification of apolipoprotein E in the cerebrospinal fluid in Alzheimer's disease
Lefranc, D., Vermersch, P., Dallongeville, J., Daems-Monpeurt, C., Petit, H., & Delacourte, A. (1996) · Neuroscience Letters · doi:10.1016/0304-3940(96)12774-9 · Cited by 47 · see citing works
Phagocytosis of Apoptotic Cells Is Specifically Upregulated in ApoE4 Expressing Microglia in vitro
Muth, C., Hartmann, A., Falla, D. S., Glatzel, M., & Krasemann, S. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00181 · Cited by 47 · see citing works
ApoE expression in macrophages communicates immunometabolic signaling that controls hyperlipidemia‐driven hematopoiesis & inflammation via extracellular vesicles
Phu, T. A., Ng, M., Vu, N. K., Gao, A. S., & Raffaı̈, R. L. (2023) · Journal of Extracellular Vesicles · doi:10.1002/jev2.12345 · Cited by 47 · see citing works
Redefining transcriptional regulation of the APOE gene and its association with Alzheimer’s disease
Lee, E.-G., Tulloch, J., Chen, S., Leong, L., Saxton, A. D., Kraemer, B. C., Darvas, M., Keene, C. D., Shutes‐David, A., Todd, K. W., et al. (2020) · PLoS ONE · doi:10.1371/journal.pone.0227667 · Cited by 46 · see citing works
Microglia depletion reduces human neuronal APOE4-related pathologies in a chimeric Alzheimer’s disease model
Rao, A. T., Chen, N., Kim, M. J., Blumenfeld, J. R., Yip, O., Liang, Z., Shostak, D. M., Hao, Y., Nelson, M. R., Koutsodendris, N., et al. (2024) · Cell stem cell · doi:10.1016/j.stem.2024.10.005 · Cited by 46 · see citing works
APOE loss-of-function variants: Compatible with longevity and associated with resistance to Alzheimer’s disease pathology
Chemparathy, A., Le Guen, Y., Chen, S., Lee, E.-G., Leong, L., Gorzynski, J. E., Jensen, T. D., Ferrasse, A., Xu, G., Xiang, H., et al. (2024) · Neuron · doi:10.1016/j.neuron.2024.01.008 · Cited by 44 · see citing works
Age-Related Changes in the Behavior of Apolipoprotein E Knockout Mice
Fuentes, D., Fernández, N., García, Y., García, T. E., Morales, A., & Menéndez, R. (2018) · Behavioral Sciences · doi:10.3390/bs8030033 · Cited by 43 · see citing works
Astrocytic and neuronal apolipoprotein E isoforms differentially affect neuronal excitability
Konings, S. C., Torres-Garcia, L., Martinsson, I., & Gouras, G. K. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.734001 · Cited by 43 · see citing works
Brain border-associated macrophages: common denominators in infection, aging, and Alzheimer’s disease?
Mesquita, S. D., & Rua, R. (2024) · Trends in Immunology · doi:10.1016/j.it.2024.03.007 · Cited by 43 · see citing works
Apolipoprotein E (apoE) levels in brains from Alzheimer disease patients and controls
Pirttilä, T., Soininen, H., Heinonen, O., Lehtimäki, T., Bogdanovic, N., Paljärvi, L., Kosunen, O., Winblad, B., Riekkinen, P., Wisniewski, H. M., et al. (1996) · Brain Research · doi:10.1016/0006-8993(96)00183-7 · Cited by 42 · see citing works
Astrocytic APOE4 removal confers cerebrovascular protection despite increased cerebral amyloid angiopathy
Xiong, M., Wang, C., Gratuze, M., Saadi, F., Bao, X., Bosch, M. E., Lee, C., Jiang, H., Serrano, J. R., Gonzales, E. R., et al. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00610-x · Cited by 41 · see citing works
APOE ε4 allele and CSF APOE on Cognition in HIV-Infected Subjects
Andres, M. A., Feger, U., Nath, A., Munsaka, S. M., Jiang, C. S., & Chang, L. (2010) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-010-9254-3 · Cited by 40 · see citing works
NAP Enhances Neurodevelopment of Newborn Apolipoprotein E-Deficient Mice Subjected to Hypoxia
Rotstein, M. S., Bassan, H., Kariv, N., Speiser, Z., Harel, S., & Gozes, I. (2006) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.106.106898 · Cited by 40 · see citing works
Cholesterol in the CNS: functions, recycling and remyelination
Wuerch, E. C., & Yong, V. W. (2025) · Journal of Neuroinflammation · doi:10.1186/s12974-025-03490-8 · Cited by 40 · see citing works
Brain integrity is altered by hepatic APOE ε4 in humanized-liver mice
Giannisis, A., Patra, K., Edlund, A. K., Nieto, L. A., Benedicto-Gras, J., Moussaud, S., de la Rosa, A., Twohig, D., Bengtsson, T., Fu, Y., et al. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01548-0 · Cited by 39 · see citing works
APOE genotype determines cell-type-specific pathological landscape of Alzheimer’s disease
Li, Z., Martens, Y. A., Ren, Y., Jin, Y., Sekiya, H., Doss, S. V., Kouri, N., Castanedes-Casey, M., Christensen, T. A., Miller Nevalainen, L. B., et al. (2025) · Neuron · doi:10.1016/j.neuron.2025.02.017 · Cited by 39 · see citing works
Silencing Apoe with divalent‐siRNAs improves amyloid burden and activates immune response pathways in Alzheimer's disease
Ferguson, C. M., Hildebrand, S. R., Godinho, B. M. D. C., Buchwald, J. E., Echeverria, D., Coles, A. H., Grigorenko, A. P., Vangjeli, L., Sousa, J., McHugh, N., et al. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.13703 · Cited by 38 · see citing works
Association of ApoE and LRP mRNA levels with dementia and AD neuropathology
Akram, A. M., Schmeidler, J., Katsel, P., Hof, P. R., & Haroutunian, V. H. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.04.010 · Cited by 37 · see citing works
Meta-analysis of apolipoprotein E levels in the cerebrospinal fluid of patients with Alzheimer's disease
Talwar, P., Sinha, J., Grover, S., Agarwal, R., Kushwaha, S. S., Srivastava, M. V. P., & Kukreti, R. (2015) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2015.12.004 · Cited by 37 · see citing works
Apolipoprotein E ε4 disrupts oligodendrocyte differentiation by interfering with astrocyte‐derived lipid transport
Mok, K. K., Yeung, S. H., Cheng, G. W., Ma, I. W., Lee, R. H., Herrup, K., & Tse, K. (2023) · Journal of Neurochemistry · doi:10.1111/jnc.15748 · Cited by 37 · see citing works
Delayed, but Marked, Expression of Apolipoprotein E is Involved in Tissue Clearance after Cerebral Infarction
Kitagawa, K., Matsumoto, M., Kuwabara, K., Ohtsuki, T., & Hori, M. (2001) · Journal of Cerebral Blood Flow and Metabolism · doi:10.1097/00004647-200110000-00008 · Cited by 36 · see citing works
Apolipoprotein E ε4 Mediates Myelin Breakdown by Targeting Oligodendrocytes in Sporadic Alzheimer Disease
Cheng, G. W.-Y., Mok, K. K.-S., Yeung, S. H.-S., Kofler, J., Herrup, K., & Tse, K.-H. (2022) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlac054 · Cited by 36 · see citing works
Apolipoprotein E (ApoE), a Bmp‐2 (bone morphogenetic protein) upregulated gene in mesenchymal progenitors (C3H10T1/2), is highly expressed in murine embryonic development
Bächner, D., Schröder, D., Betat, N., Ahrens, M., & Gross, G. (1999) · BioFactors · doi:10.1002/biof.5520090103 · Cited by 35 · see citing works
Isoform-specific effects of apoE on neurite outgrowth in olfactory epithelium culture
Hussain, A., Luong, M., Pooley, A., & Nathan, B. P. (2013) · Journal of Biomedical Science · doi:10.1186/1423-0127-20-49 · Cited by 34 · see citing works
Apolipoprotein E Regulates Injury-Induced Activation of Hippocampal Neural Stem and Progenitor Cells
Hong, S. J., Washington, P. M., Kim, A., Yang, C.-P., Yu, T., & Kernie, S. G. (2015) · Journal of Neurotrauma · doi:10.1089/neu.2014.3860 · Cited by 33 · see citing works
Astrocytic ApoE underlies maturation of hippocampal neurons and cognitive recovery after traumatic brain injury in mice
Yu, T., Tensaouti, Y., Stephanz, E. P., Chintamen, S., Rafikian, E. E., Yang, M., & Kernie, S. G. (2021) · Communications Biology · doi:10.1038/s42003-021-02841-4 · Cited by 33 · see citing works
Up-regulation of apolipoprotein E by leptin in the hypothalamus of mice and rats
Shen, L., Tso, P., Wang, D. Q. ‐., Woods, S. C., Davidson, W. S., Sakai, R. R., & Liu, M. (2009) · Physiology & Behavior · doi:10.1016/j.physbeh.2009.05.013 · Cited by 32 · see citing works
Impact of Apolipoprotein E gene polymorphism during normal and pathological conditions of the brain across the lifespan
Iacono, D., & Feltis, G. C. (2019) · Aging · doi:10.18632/aging.101757 · Cited by 32 · see citing works
APOE from astrocytes restores Alzheimer’s Aβ-pathology and DAM-like responses in APOE deficient microglia
Preman, P., Moechars, D., Fertan, E., Wolfs, L., Serneels, L., Shah, D., Lamote, J., Poovathingal, S., Snellinx, A., Mancuso, R., et al. (2024) · EMBO Molecular Medicine · doi:10.1038/s44321-024-00162-7 · Cited by 32 · see citing works
Multi-functional role of apolipoprotein E in neurodegenerative diseases
Islam, S., Noorani, A., Sun, Y., Michikawa, M., & Zou, K. (2025) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2025.1535280 · Cited by 30 · see citing works
Therapeutic potential of ApoE-mimetic peptides in CNS disorders: Current perspective
Ahmed, S., Pande, A. H., & Sharma, S. S. (2022) · Experimental Neurology · doi:10.1016/j.expneurol.2022.114051 · Cited by 27 · see citing works
The APOE isoforms differentially shape the transcriptomic and epigenomic landscapes of human microglia xenografted into a mouse model of Alzheimer's disease
Murphy, K. B., Hu, D., Wolfs, L., Rohde, S. K., Fauró, G. L., Geric, I., Mancuso, R., De Strooper, B., & Marzi, S. J. (2025) · Nature Communications · doi:10.1038/s41467-025-60099-4 · Cited by 25 · see citing works
Independent <scp> APOE4 </scp> knock‐in mouse models display reduced brain <scp>APOE</scp> protein, altered neuroinflammation, and simplification of dendritic spines
Sepulveda, J., Luo, N., Nelson, M., Ng, C. A. S., & Rebeck, G. W. (2022) · Journal of Neurochemistry · doi:10.1111/jnc.15665 · Cited by 24 · see citing works
The proportion of Alzheimer’s disease attributable to apolipoprotein E
Williams, D. M., Heikkinen, S., Hiltunen, M. O., FinnGen, Davies, N. M., & Anderson, E. L. (2026) · npj Dementia · doi:10.1038/s44400-025-00045-9 · Cited by 23 · see citing works
Spatiotemporal changes of apolipoprotein E immunoreactivity and apolipoprotein E mRNA expression after transient middle cerebral artery occlusion in rat brain
Kamada, H., Sato, K., Zhang, W. R., Omori, N., Nagano, I., Shoji, M., & Abe, K. (2003) · Journal of Neuroscience Research · doi:10.1002/jnr.10658 · Cited by 22 · see citing works
Age-related Alterations of Apolipoprotein E and Interleukin-1β in the Aging Brain
Gee, J. R., Ding, Q., & Keller, J. N. (2006) · Biogerontology · doi:10.1007/s10522-005-6039-9 · Cited by 21 · see citing works
Differential associations between apolipoprotein E alleles and cerebral myelin content in normative aging
Triebswetter, C., Kiely, M., Khattar, N., Ferrucci, L., Resnick, S., Spencer, R. G., & Bouhrara, M. (2022) · NeuroImage · doi:10.1016/j.neuroimage.2022.118988 · Cited by 19 · see citing works
Apolipoprotein E imbalance in the cerebrospinal fluid of Alzheimer’s disease patients
Lennol, M. P., Sánchez-Domínguez, I., Cuchillo‐Ibáñez, I., Camporesi, E., Brinkmalm, G., Alcolea, D. A., Fortea, J., Lleó, A., Sòria, G., Aguado, F., et al. (2022) · Alzheimer s Research & Therapy · doi:10.1186/s13195-022-01108-2 · Cited by 19 · see citing works
APOE4 impacts cortical neurodevelopment and alters network formation in human brain organoids
Meyer-Acosta, K. K., Díaz‐Guerra, E., Varma, P., Aruk, A., Mirsadeghi, S., Perez, A. M., Rafati, Y., Hosseini, A., Nieto‐Estévez, V., Giugliano, M., et al. (2025) · Stem Cell Reports · doi:10.1016/j.stemcr.2025.102537 · Cited by 19 · see citing works
Human apolipoprotein E glycosylation and sialylation: from structure to function
Moon, H.-J., Luo, Y., Chugh, D., & Zhao, L. (2024) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2024.1399965 · Cited by 18 · see citing works
Emerging Role of Oligodendrocytes Malfunction in the Progression of Alzheimer's Disease
Tylek, K., & Basta‐Kaim, A. (2025) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-025-10236-z · Cited by 18 · see citing works
APOE4 to APOE2 allelic switching in mice improves Alzheimer’s disease-related metabolic signatures, neuropathology and cognition
Golden, L. R., Siano, D. S., Stephens, I. O., MacLean, S. M., Saito, K., Nolt, G. L., Funnell, J. L., Pallerla, A. V., Lee, S., Smith, C., et al. (2025) · Nature Neuroscience · doi:10.1038/s41593-025-02094-y · Cited by 18 · see citing works
Self-citation
Repetitive head trauma and apoE4 induce chronic cerebrovascular alterations that impair tau elimination from the brain
Eisenbaum, M., Pearson, A., Ortiz, C., Koprivica, M., Cembran, A., MULLAN, M. J., Crawford, F., Ojo, J. O., & Bachmeier, C. J. (2024) · Experimental Neurology · doi:10.1016/j.expneurol.2024.114702 · Cited by 17 · see citing works
Astrocyte Lipid Droplet Dynamics Orchestrate Neurological Disorders and Therapeutic Horizons
Zhong, J., Peng, Y., Zhang, L., Xiao, B., & Zhang, M. (2025) · Small Science · doi:10.1002/smsc.202500152 · Cited by 16 · see citing works
APOE-Targeted Therapeutics for Alzheimer's Disease
Yassine, H. N., Hugo, C., O’Donovan, B., Stephens, I. O., Johnson, L. A., Cole, G. M., Julia, T. C. W., Johansson, J. O., Kisler, K., & Chiba‐Falek, O. (2025) · Journal of Neuroscience · doi:10.1523/jneurosci.1388-25.2025 · Cited by 16 · see citing works
Self-citation
Isoform- and cell-state-specific APOE homeostasis and function
Lindner, K., & Gavin, A.-C. (2024) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-23-01470 · Cited by 13 · see citing works
Up-regulation of low-density lipoprotein receptor expression in the ischemic core and the peri-ischemic area after transient MCA occlusion in rats
Kamada, H., Hayashi, T., Sato, K., Iwai, M., Nagano, I., Shoji, M., & Abe, K. (2005) · Molecular Brain Research · doi:10.1016/j.molbrainres.2004.10.037 · Cited by 12 · see citing works
Food-entrained rhythmic expression of apolipoprotein E expression in the hypothalamus of rats
Shen, L., Carey, K., Wang, D. Q. ‐., Woods, S. C., & Liu, M. (2009) · Brain Research · doi:10.1016/j.brainres.2009.04.004 · Cited by 12 · see citing works
Age-Dependent Expression of Apolipoprotein E in Mouse Cerebral Cortex
Singh, S., & Thakur, M. K. (2010) · Journal of Molecular Neuroscience · doi:10.1007/s12031-010-9412-3 · Cited by 10 · see citing works
Towards an Understanding of Microglia and Border-Associated Macrophages
Taketomi, T., & Tsuruta, F. (2023) · Biology · doi:10.3390/biology12081091 · Cited by 10 · see citing works
Border-associated macrophages: an emerging perspective from physiological basis and multi-disease roles to the mechanism of vascular cognitive impairment and dementia
Li, T., Zhang, J., Song, H., Zhang, R., Fan, F., Huang, Z., Zeng, M., Peng, B., & Zhang, J. (2025) · Journal of Neuroinflammation · doi:10.1186/s12974-025-03631-z · Cited by 10 · see citing works
The absorption of apolipoprotein E by damaged neurons facilitates neuronal repair
Chen, M., Xie, M., Peng, C., & Long, S. (2019) · Cell Biology International · doi:10.1002/cbin.11135 · Cited by 9 · see citing works
Apolipoprotein E abundance is elevated in the brains of individuals with Down syndrome–Alzheimer’s disease
Farrell, C., Buhidma, Y., Mumford, P., Heywood, W. E., Hällqvist, J., Flores-Aguilar, L., Andrews, E. J., Rahimzadah, N., Taso, O. S., Doran, E., et al. (2025) · Acta Neuropathologica · doi:10.1007/s00401-025-02889-0 · Cited by 9 · cited 1× · see citing works
“…with Down syndrome–associated AD (DSAD) show increased apoE protein in the prefrontal cortex compared to both healthy controls and matched early onset AD cases, with upregulation observed in astrocytes, endothelial cells, and pericytes; these changes occur independently of APOE genotype [177].”
Apolipoprotein E expression pattern in human induced pluripotent stem cells during in vitro neural induction
Lee, H. A., Cocks, G. D., Nowosiad, P., Polit, L. D., Price, J., Srivas, D. P., & Thuret, S. (2020) · F1000Research · doi:10.12688/f1000research.23580.2 · Cited by 8 · see citing works
Microglia Depletion Reduces Human Neuronal APOE4-Driven Pathologies in a Chimeric Alzheimer’s Disease ModelPreprint
Rao, A. T., Chen, N., Kim, M. J., Blumenfeld, J. R., Yip, O., Hao, Y., Liang, Z., Nelson, M. R., Koutsodendris, N., Grone, B. P., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.11.10.566510 · Cited by 8 · see citing works
Single-nucleus RNA sequencing reveals the specific molecular signatures of myeloid cells responding to brain injury after microglial replacement
Xiong, X.-Y., Yuan, H., Mu, Y., He, Y., Xie, F., Feng, X., Xie, J., Pan, X., Wang, Y.-F., Gong, J., et al. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1625673 · Cited by 8 · see citing works
Apolipoprotein E aggregation in microglia initiates Alzheimer’s disease pathology by seeding β-amyloidosis
Kaji, S., Berghoff, S. A., Spieth, L., Schlaphoff, L., Sasmita, A. O., Vitale, S., Büschgens, L., Kedia, S., Zirngibl, M., Nazarenko, T., et al. (2025) · Immunity · doi:10.1016/j.immuni.2024.11.024 · Cited by 7 · see citing works
APOE genotypes differentially remodel the astrocytic lipid droplet-associated proteome to shape lipid droplet dynamicsPreprint
Cuní‐López, C., Root, J. T., Hao, Y., Kowal, I., Blomberg, N., Ghirlando, R., Yang, L. G., Hertog, S. K.-D., Cookson, M., van der Kant, R., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.08.19.669163 · Cited by 7 · see citing works
APOE genotype-dependent differences in human astrocytic energy metabolism
Budny, V., Bodenmann, C., Zürcher, K. J., Krüger, M., de Leeuw, S. M., Weber, R. Z., Rust, R., Ravotto, L., Ruminot, I., Barros, L. F., et al. (2025) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2025.1603657 · Cited by 6 · see citing works
APOE3 astrocytes can rescue lipid abnormalities and dystrophic neurites of APOE4 human neurons
Halim, D. O., Biase, E. D., Rajon, A., Jordi, L., Hallett, P. J., & Ole Isacson, A. (2026) · PNAS Nexus · doi:10.1093/pnasnexus/pgag053 · Cited by 6 · see citing works

Flagged first, then by citations

Research works printed but not linked: 1

[135]Iadecola C, et al. Cell autonomous role of border associated macrophages in ApoE4 neurovascular dysfunction and susceptibility to white matter injury. Res Sq. 2023. PMC11758676 39294490

Sorted by citations

Heart and Brain: Linking Obesity-Related Inflammation, Cardiovascular Disease and Cognitive Function
Reiss, A. B., Gulkarov, S., Syed, U., Ben-Dor, G. A., Srivastava, A., Singh, M., & Leon, J. D. (2026) · Journal of Cardiovascular Development and Disease · doi:10.3390/jcdd13100477
Apolipoproteins in nanoparticle-mediated brain drug delivery: promise, mechanisms, and misconceptions
Gelperina, S. E., & Wacker, M. G. (2026) · Expert Opinion on Drug Delivery · doi:10.1080/17425247.2026.2755180

S3‐02–05: APOE expression in different types of cells in the CNS: Roles in neurobiology and Alzheimer's disease
Huang, Y. (2008) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2008.05.382
O4–01–05: Profile and regulation of APOE expression in central nervous system in mice with targeting of green fluorescent protein gene to the APOE locus
Xu, Q., Bernardo, A., Walker, D., Kanegawa, T., Mahley, R. W., & Huang, Y. (2006) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2006.05.295
Profile and Regulation of Apolipoprotein E (ApoE) Expression in the CNS in Mice with Targeting of Green Fluorescent Protein Gene to the ApoE Locus
Xu, Q., Bernardo, A., Walker, D., Kanegawa, T., Mahley, R. W., & Huang, Y. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.5476-05.2006 · Cited by 524 · see citing works
Expression and regulation of apolipoprotein E receptors in the cells of the central nervous system in culture: A review
Fan, Q.-W., Iosbe, I., Asou, H., Yanagisawa, K., & Michikawa, M. (2001) · Journal of the American Aging Association · doi:10.1007/s11357-001-0001-9 · Cited by 47 · see citing works
Apolipoprotein E elicits target-directed miRNA degradation to maintain neuronal integrity
Tan, J., & Ong, C.-T. (2024) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-24-00680 · Cited by 1 · see citing works

Authors: Nolt, G. L., Lucido, C. C., Smith, L. M., & Johnson, L. A.
Affiliations: University of Kentucky (US)
Corresponding author: Johnson, Lance A.
ORCID: Nolt, Georgia L.
Lucido, Chloe C.
Smith, Lily M.
Johnson, Lance A.
Venue: Molecular Neurodegeneration Advances
Publisher: Springer Science and Business Media LLC
Published: 2026-04-17
Volume: 2
Issue: 1
Pages: 24-24
ISSN: 3059-4944 (ISSN-L)
DOI: 10.1186/s44477-026-00028-x
PMC: PMC13216210
OpenAlex: W7154709482
Cited by: 2
References: 193
Citations by year: 2026: 2
FWCI: 2.09
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-nd
creativecommons.org/licenses/by-nc-nd/4.0 (tdm)
creativecommons.org/licenses/by-nc-nd/4.0 (vor, 41 d)
Locations: Molecular Neurodegeneration Advances (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
PubMed Central (publishedVersion, cc-by-nc-nd)
Funders: National Institutes of Health (R01AG081421)
National Institute of General Medical Sciences (COBRE P20 GM148326)
Alzheimer's Association (ABA-22-972169)
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Keywords: apolipoprotein E, APOE isoforms, Alzheimer's disease, central nervous system, astrocytes, microglia, oligodendrocyte lineage, spatiotemporal gene expression, post-transcriptional regulation, aging, neuroinflammation

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

ApoE expression across the CNS: Who, What, Where, When, and How (much)?

Abstract

Integrity signals

Claims the paper makes

Self-check

Cites

Cited by

Related

Record

About these checks