Cited by 140Alzheimer's disease research and treatmentsCellular transport and secretionAutophagy in Disease and Therapy

The DOI matches its Crossref record; 59 of the 59 references it cites were found in a registry or an index.

The endosomal-lysosomal pathway is dysregulated by APOE4 expression in vivo

Open access

Nuriel, Tal, Peng, Katherine Y., Ashok, Archana, Dillman, Allissa A., Figueroa, Helen Y., Apuzzo, Justin, Ambat, Jayanth, Levy, Efrat, Cookson, Mark R., Mathews, Paul M., Duff, Karen E.·2017·Frontiers in Neuroscience

DOI 10.3389/fnins.2017.00702PMC PMC5733017

Open this paper in CoChat — free account Open PDF

Abstract

Possession of the ε4 allele of apolipoprotein E (APOE) is the major genetic risk factor for late-onset Alzheimer’s disease (AD). Although numerous hypotheses have been proposed, the precise cause of this increased AD risk is not yet known. In order to gain a more comprehensive understanding of APOE4's role in AD, we performed RNA-sequencing on an AD-vulnerable vs. an AD-resistant brain region from aged APOE targeted replacement mice. This transcriptomics analysis revealed a significant enrichment of genes involved in endosomal-lysosomal processing, suggesting an APOE4-specific endosomal-lysosomal pathway dysregulation in the brains of APOE4 mice. Further analysis revealed clear differences in the morphology of endosomal-lysosomal compartments, including an age-dependent increase in the number and size of early endosomes in APOE4 mice. These findings directly link the APOE4 genotype to endosomal-lysosomal dysregulation in an in vivo, AD pathology-free setting, which may play a causative role in the increased incidence of AD among APOE4 carriers.

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 · 10.3389/fnins.2017.00702

Cites

59 of 59 references verified0 citation errors · 0 not checkable

Statistics

Figure 1 Transcriptomics analysis was performed on RNA extracted from the EC and PVC of aged APOE3/4 vs. APOE3/3 mice. RNA-sequencing was performed to analyze the effects of differential APOE isoform expression on RNA levels in the PVC and EC of aged APOE mice APOE3/4 (19 APOE3/4 males vs. 10 APOE3/3 males). (A) A heat map visualizing the Euclidean distance between samples, with darker red colors indicating increased similarity. (B) Volcano plots visualizing the fold change and adjusted p-values of each gene that was differentially expressed in the PVC and EC of APOE3/4 vs. APOE3/3 mice.CC BY · PubMed Central

Figure 2 Pathway analysis reveals numerous pathways affected by differential APOE isoform expression. A pathway analysis was performed on the differentially expressed EC genes using Cytoscape's ClueGo application. Shown here are the significantly enriched KEGG pathways observed in the EC of APOE3/4 vs. APOE3/3 mice, with the 9 differentially expressed V-type ATPase genes circled. (Further details can be found in Table 1).CC BY · PubMed Central

Figure 3 Genes related to endosomal–lysosomal system function are upregulated in the EC of APOE3/4 mice. Our RNA-Seq analysis of EC genes from aged APOE3/4 vs. APOE3/3 mice revealed an enrichment of upregulated genes related to endosomal–lysosomal system function. (A) Differentially regulated V-type ATPases in the EC of APOE3/4 vs. APOE3/3 mice. (B) Differentially regulated Rab GTPases in the EC of APOE3/4 vs. APOE3/3 mice. (**p < 0.01; ***p < 0.001; ****p < 0.0001).CC BY · PubMed Central

Figure 4 The number and area fraction of Rab5a- and CatD-immunoreactive compartments are increased in the EC of aged APOE4/4 vs. APOE3/3 mice. Rab5a-immunoreactive early endosomes and CatD-immunoreactive lysosomes were quantified in the entorhinal cortex of 18 month-old APOE3/3 and APOE4/4 mice. (A) Representative images showing Rab5a and CatD immunolabeling (red), co-stained with Nissl (green). Black and white images were generated in ImageJ and used for quantification. (B–D) Quantification of average Rab5a- and CatD-positive compartment number (B), size (C), and area fraction (D) in APOE4/4 vs. APOE3/3 mice. (*p < 0.05; ***p < 0.001).CC BY · PubMed Central

Figure 5 The number, size and area fraction of Rab5a-immunoreactive early endosomes are increased in the cingulate cortex of APOE4/4 vs. APOE3/3 mice with age. Rab5a-immunoreactive early endosomes were quantified in the cingulate cortex of 6, 12, 18, and 25 month-old APOE3/3 and APOE4/4 mice. (A) Representative images showing Rab5a immunolabeling (red). Black and white images were generated in ImageJ and used for quantification. (B–D) Quantification of average Rab5a-positive early endosome number (B), size (C), and area fraction (D) in APOE4/4 vs. APOE3/3 mice. (***p < 0.001; findings are normalized to the mean APOE3/3 value at each age in order to compare between age groups).CC BY · PubMed Central

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.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

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

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

Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123
Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI.
Hixson, J., & Vernier, D. (1990) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)43176-1 · Cited by 2,933
The role of the posterior cingulate cortex in cognition and disease
Leech, R., & Sharp, D. J. (2014) · Brain · doi:10.1093/brain/awt162 · Cited by 2,247
Apolipoprotein E: Far More Than a Lipid Transport Protein
Mahley, R. W., & Rall, S. C. (2000) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev.genom.1.1.507 · Cited by 1,836
Metabolic reduction in the posterior cingulate cortex in very early Alzheimer's disease
Minoshima, S., Giordani, B., Berent, S., Frey, K. A., Foster, N. L., & Kuhl, D. E. (1997) · Annals of Neurology · doi:10.1002/ana.410420114 · Cited by 1,802
Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease.
Schmechel, D. E., Saunders, A. M., Strittmatter, W. J., Crain, B. J., Hulette, C. M., Joo, S. H., Pericak-Vance, M. A., Goldgaber, D., & Roses, A. D. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.20.9649 · Cited by 1,525
Preclinical Evidence of Alzheimer's Disease in Persons Homozygous for the ε4 Allele for Apolipoprotein E
Reiman, E. M., Caselli, R. J., Yun, L. S., Chen, K., Bandy, D., Minoshima, S., Thibodeau, S. N., & Osborne, D. (1996) · New England Journal of Medicine · doi:10.1056/nejm199603213341202 · Cited by 1,366
Human ApoE isoforms differentially regulate brain amyloid-β peptide clearance
Castellano, J. M., Kim, J., Stewart, F. R., Jiang, H., DeMattos, R. B., Patterson, B. W., Fagan, A. M., Morris, J. C., Mawuenyega, K. G., Cruchaga, C., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002156 · Cited by 1,242 · cited 2×
“While APOE4’s role in AD has often been attributed to its ability to increase the aggregation and decrease the clearance of Aβ (Rebeck et al., 1993; Schmechel et al., 1993; Ma et al., 1994; Castano et al., 1995; Bales et al., 1997; Holtzman et al., 2000; Castellano et al., 2011), APOE4 expression has also been shown t…”
Background
Amyloid Precursor Protein Trafficking, Processing, and Function
Thinakaran, G., & Koo, E. H. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.r800019200 · Cited by 1,141
Apolipoprotein E in sporadic Alzheimer's disease: Allelic variation and receptor interactions
William Rebeck, G., Reiter, J. S., Strickland, D. K., & Hyman, B. T. (1993) · Neuron · doi:10.1016/0896-6273(93)90070-8 · Cited by 1,107

Show all 59 references

Sorted by citations

Apolipoprotein E and Alzheimer disease: pathobiology and targeting strategies
Yamazaki, Y., Zhao, N., Caulfield, T. R., Liu, C.-C., & Bu, G. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0228-7 · Cited by 1,425
Down syndrome
Antonarakis, S. E., Skotko, B. G., Rafii, M. S., Strydom, A., Pape, S. E., Bianchi, D. W., Sherman, S. L., & Reeves, R. H. (2020) · Nature Reviews Disease Primers · doi:10.1038/s41572-019-0143-7 · Cited by 964
Amyloid-β-independent regulators of tau pathology in Alzheimer disease
van der Kant, R., Goldstein, L. S. B., & Ossenkoppele, R. (2020) · Nature reviews. Neuroscience · doi:10.1038/s41583-019-0240-3 · Cited by 580
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
Hypothesis: Tau pathology is an initiating factor in sporadic Alzheimer's disease
Arnsten, A. F. T., Datta, D., Del Tredici, K., & Braak, H. (2021) · Alzheimer's & Dementia · doi:10.1002/alz.12192 · Cited by 361
ApoE Cascade Hypothesis in the pathogenesis of Alzheimer’s disease and related dementias
Martens, Y. A., Zhao, N., Liu, C.-C., Kanekiyo, T., Yang, A. J., Goate, A. M., Holtzman, D. M., & Bu, G. (2022) · Neuron · doi:10.1016/j.neuron.2022.03.004 · Cited by 316
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
Lipid droplets in the nervous system
Ralhan, I., Chang, C.-L., Lippincott-Schwartz, J., & Ioannou, M. S. (2021) · Journal of Cell Biology · doi:10.1083/jcb.202102136 · Cited by 281
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
The Role of APOE4 in Disrupting the Homeostatic Functions of Astrocytes and Microglia in Aging and Alzheimer’s Disease
Fernandez, C. G., Hamby, M. E., McReynolds, M. L., & Ray, W. J. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00014 · Cited by 277
Apolipoprotein E and Alzheimer’s disease: Findings, hypotheses, and potential mechanisms
Koutsodendris, N., Nelson, M. R., Rao, A., & Huang, Y. (2022) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathmechdis-030421-112756 · Cited by 231
Mitophagy in Human Diseases
Doblado, L., Lueck, C., Rey, C., Samhan-Arias, A. K., Priéto, I., Stacchiotti, A., & Monsalve, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22083903 · Cited by 238
Endo-lysosomal dysregulations and late-onset Alzheimer’s disease: impact of genetic risk factors
Van Acker, Z. P., Bretou, M., & Annaert, W. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0323-7 · Cited by 222
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
APOE4 is associated with cognitive and pathological heterogeneity in patients with Alzheimer’s disease: a systematic review
Emrani, S., Arain, H. A., DeMarshall, C. A., & Nuriel, T. (2020) · Alzheimer s Research & Therapy · doi:10.1186/s13195-020-00712-4 · Cited by 207
Self-citation
Ultrasound-mediated augmented exosome release from astrocytes alleviates amyloid-β-induced neurotoxicity
Deng, Z., Wang, J., Xiao, Y., Li, F., Niu, L., Liu, X., Meng, L., & Zheng, H. (2021) · Theranostics · doi:10.7150/thno.52436 · Cited by 171
ApoE4 Alters ABCA1 Membrane Trafficking in Astrocytes
Rawat, V., Wang, S., Sima, J., Bar, R., Liraz, O., Gundimeda, U., Parekh, T., Chan, J., Johansson, J. O., Tang, C., et al. (2019) · The Journal of Neuroscience · doi:10.1523/jneurosci.1400-19.2019 · Cited by 165
Expression and secretion of apoE 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
Apolipoprotein E and Alzheimer's disease
Troutwine, B., Hamid, L., Lysaker, C. R., Strope, T. A., & Wilkins, H. (2021) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2021.10.002 · Cited by 179
Isolation of mitochondria-derived mitovesicles and subpopulations of microvesicles and exosomes from brain tissues
D’Acunzo, P., Kim, Y., Ungania, J. M., Pérez‐González, R., Goulbourne, C. N., & Levy, E. (2022) · Nature Protocols · doi:10.1038/s41596-022-00719-1 · Cited by 162
Self-citation
APOE alleles and diet in brain aging and Alzheimer's disease
Yassine, H. N., & Finch, C. E. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.00150 · Cited by 145
TREM2-independent microgliosis promotes tau-mediated neurodegeneration in the presence of ApoE4.
Gratuze, M., Schlachetzki, J. C. M., D’Oliveira Albanus, R., Jain, N., Novotny, B., Brase, L., Rodriguez, L., Mansel, C., Kipnis, M., O’Brien, S., et al. (2023) · Neuron · doi:10.1016/j.neuron.2022.10.022 · Cited by 115
Apolipoprotein E4 genotype compromises brain exosome production
Peng, K. Y., Pérez-González, R., Alldred, M. J., Goulbourne, C. N., Morales-Corraliza, J., Saito, M., Saito, M., Ginsberg, S. D., Mathews, P. M., & Levy, E. (2019) · Brain · doi:10.1093/brain/awy289 · Cited by 109
Self-citation
APOE2, E3, and E4 differentially modulate cellular homeostasis, cholesterol metabolism, and inflammatory response in isogenic iPSC-derived astrocytes
de Leeuw, S. M., Kirschner, A. W. T., Lindner, K., Rust, R., Budny, V., Wolski, W. E., Gavin, A.-C., Nitsch, R. M., & Tackenberg, C. (2022) · Stem Cell Reports · doi:10.1016/j.stemcr.2021.11.007 · Cited by 105
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
Preserving Lysosomal Function in the Aging Brain: Insights from Neurodegeneration
Peng, W., Minakaki, G., Nguyen, M., & Krainc, D. (2019) · Neurotherapeutics · doi:10.1007/s13311-019-00742-3 · Cited by 79
Alzheimer’s-like pathology in aging rhesus macaques: Unique opportunity to study the etiology and treatment of Alzheimer’s disease
Arnsten, A. F. T., Datta, D., Leslie, S., Yang, S.-T., Wang, M., & Nairn, A. C. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1903671116 · Cited by 74
Endo-lysosomal pathway and ubiquitin-proteasome system dysfunction in Alzheimer's disease pathogenesis
Cao, J., Zhong, M. B., Toro, C. A., Zhang, L., & Cai, D. (2019) · Neuroscience Letters · doi:10.1016/j.neulet.2019.03.016 · Cited by 82
Exosome Production Is Key to Neuronal Endosomal Pathway Integrity in Neurodegenerative Diseases
Mathews, P. M., & Levy, E. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.01347 · Cited by 81
Self-citation
PICALM Rescues Endocytic Defects Caused by the Alzheimer’s Disease Risk Factor APOE4
Narayan, P., Sienski, G., Bonner, J. M., Lin, Y.-T., Seo, J., Baru, V., Haque, A., Milo, B., Akay, L. A., Graziosi, A., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108224 · Cited by 75
Phospholipase D3 degrades mitochondrial DNA to regulate nucleotide signaling and APP metabolism
Acker, Z. P. V., Perdok, A., Hellemans, R., North, K., Vorsters, I., Cappel, C. C., Dehairs, J., Swinnen, J. V., Sannerud, R., Bretou, M., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-38501-w · Cited by 76
Apolipoprotein E in Alzheimer’s disease trajectories and the next-generation clinical care pathway
Narasimhan, S., Holtzman, D. M., Apostolova, L. G., Cruchaga, C., Masters, C. L., Hardy, J., Villemagne, V. L., Bell, J. S., Cho, M., & Hampel, H. J. (2024) · Nature Neuroscience · doi:10.1038/s41593-024-01669-5 · Cited by 70
Reassessment of Pioglitazone for Alzheimer’s Disease
Saunders, A. M., Burns, D. K., & Gottschalk, W. K. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.666958 · Cited by 71
The synthetic TRPML1 agonist ML-SA1 rescues Alzheimer-related alterations of the endosomal-autophagic-lysosomal system
Somogyi, A., Kirkham, E. D., Lloyd‐Evans, E., Winston, J., Allen, N. D., Mackrill, J. J., Anderson, K. E., Hawkins, P. T., Gardiner, S. E., Waller‐Evans, H., et al. (2023) · Journal of Cell Science · doi:10.1242/jcs.259875 · Cited by 65
Effects of APOE4 allelic dosage on lipidomic signatures in the entorhinal cortex of aged mice
Miranda, A. M., Ashok, A., Chan, R. B., Zhou, B., Xu, Y., McIntire, L. B., Area-Gomez, E., Di Paolo, G., Duff, K. E., Oliveira, T. G., et al. (2022) · Translational Psychiatry · doi:10.1038/s41398-022-01881-6 · Cited by 60
“This suggests that while some effects of APOE4 expression may be regionally restricted, others are common throughout the brain, including previously described effects of APOE4 expression on endosomal-lysosomal trafficking [33, 53].”
BackgroundInfluentialSelf-citation
Sex-dependent calcium hyperactivity due to lysosomal-related dysfunction in astrocytes from APOE4 versus APOE3 gene targeted replacement mice
Larramona-Arcas, R., González-Arias, C., Perea, G., Gutiérrez, A., Vitorica, J., García-Barrera, T., Gómez-Ariza, J. L., Pascua-Maestro, R., Ganfornina, M. D., Kara, E., et al. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00382-8 · Cited by 56
APOE4 is Associated with Differential Regional Vulnerability to Bioenergetic Deficits in Aged APOE Mice
Area-Gomez, E., Larrea, D., Pera, M., Agrawal, R. R., Guilfoyle, D. N., Pirhaji, L., Shannon, K., Arain, H. A., Ashok, A., Chen, Q., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-61142-8 · Cited by 55
Self-citation
Cell-type-specific regulation of APOE and CLU levels in human neurons by the Alzheimer’s disease risk gene SORL1
Lee, H., Aylward, A. J., Pearse, R. V., Lish, A. M., Hsieh, Y.-C., Augur, Z. M., Benoit, C. R., Chou, V., Knupp, A., Pan, C., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112994 · Cited by 58
Apolipoprotein E deficiency exacerbates spinal cord injury in mice: inflammatory response and oxidative stress mediated by NF-κB signaling pathway
Yang, X., Chen, S., Shao, Z., Li, Y., Wu, H., Li, X., Mao, L., Zhou, Z., Bai, L., Mei, X., et al. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00142 · Cited by 52
Effect of APOE alleles on the glial transcriptome in normal aging and Alzheimer’s disease
Serrano-Pozo, A., Li, Z., Noori, A., Nguyen, H. N., Mezlini, A., Li, L., Hudry, E., Jackson, R. J., Hyman, B. T., & Das, S. (2021) · Nature Aging · doi:10.1038/s43587-021-00123-6 · Cited by 49
Exploring the Dynamic Changes of Brain Lipids, Lipid Rafts, and Lipid Droplets in Aging and Alzheimer’s Disease
Cerasuolo, M., Di Meo, I., Auriemma, M. C., Paolisso, G., Papa, M., & Rizzo, M. R. (2024) · Biomolecules · doi:10.3390/biom14111362 · Cited by 47
NHE6 depletion corrects ApoE4-mediated synaptic impairments and reduces amyloid plaque load
Pohlkamp, T., Xian, X., Wong, C. H., Durakoglugil, M. S., Werthmann, G. C., Saido, T. C., Evers, B. M., White, C. L., Connor, J., Hammer, R. E., et al. (2021) · eLife · doi:10.7554/elife.72034 · Cited by 46
A multi‐hit hypothesis for an APOE4 ‐dependent pathophysiological state
Steele, O. G., Stuart, A. C., Minkley, L., Shaw, K., Bonnar, O., Anderle, S., Penn, A. C., Rusted, J., Serpell, L., Hall, C., et al. (2022) · European Journal of Neuroscience · doi:10.1111/ejn.15685 · Cited by 44
Perspectives on ROCK2 as a Therapeutic Target for Alzheimer’s Disease
Weber, A. J., & Herskowitz, J. H. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.636017 · Cited by 42
Astrocyte in Neurological Disease: Pathogenesis and Therapy
Huang, M., Long, A., Hao, L., Shi, Z., & Zhang, M. (2025) · MedComm · doi:10.1002/mco2.70299 · Cited by 55
P38α MAPK Signaling—A Robust Therapeutic Target for Rab5-Mediated Neurodegenerative Disease
Germann, U. A., & Alam, J. J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21155485 · Cited by 40
Cellular senescence induced by cholesterol accumulation is mediated by lysosomal ABCA1 in APOE4 and AD
Wang, S., Li, B., Li, J., Cai, Z., Hugo, C., Sun, Y. E., Qian, L., Julia, T. C. W., Chui, H. C., Dikeman, D., et al. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00802-7 · Cited by 55
Brain transcriptome analysis reveals subtle effects on mitochondrial function and iron homeostasis of mutations in the SORL1 gene implicated in early onset familial Alzheimer’s disease
Barthelson, K., Pederson, S., Newman, M., & Lardelli, M. T. (2020) · Molecular Brain · doi:10.1186/s13041-020-00681-7 · Cited by 39
Deep learning of gene relationships from single cell time-course expression data
Yuan, Y., & Bar‐Joseph, Z. (2021) · Briefings in Bioinformatics · doi:10.1093/bib/bbab142 · Cited by 41
Sex Differentially Alters Secretion of Brain Extracellular Vesicles During Aging: A Potential Mechanism for Maintaining Brain Homeostasis
Kim, Y., Pérez‐González, R., Miller, C., Kurz, M., D’Acunzo, P., Goulbourne, C. N., & Levy, E. (2022) · Neurochemical Research · doi:10.1007/s11064-022-03701-1 · Cited by 42
Self-citation
Finding memo: versatile interactions of the VPS10p-Domain receptors in Alzheimer’s disease
Salasova, A., Monti, G., Andersen, O. M., & Nykjaer, A. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00576-2 · Cited by 42
Lysosomal acidification impairment in astrocyte-mediated neuroinflammation
Zeng, J., Indajang, J., Pitt, D., & Lo, C. H. (2025) · Journal of Neuroinflammation · doi:10.1186/s12974-025-03410-w · Cited by 44
The role of exosome lipids in central nervous system diseases
Wang, G., Wang, Y., Liu, N., & Liu, M. (2020) · Reviews in the Neurosciences · doi:10.1515/revneuro-2020-0013 · Cited by 34
Advancements in APOE and dementia research: Highlights from the 2023 AAIC Advancements: APOE conference
Kloske, C. M., Belloy, M. E., Blue, E. E., Bowman, G. R., Carrillo, M. C., Chen, X., Chiba‐Falek, O., Davis, A. A., Paolo, G. D., Garretti, F., et al. (2024) · Alzheimer's & Dementia · doi:10.1002/alz.13877 · Cited by 33
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
Isoform-dependent lysosomal degradation and internalization of apolipoprotein E requires autophagy proteins
Fote, G. M., Geller, N. R., Efstathiou, N. E., Hendricks, N., Vavvas, D. G., Reidling, J. C., Thompson, L. M., & Steffan, J. S. (2022) · Journal of Cell Science · doi:10.1242/jcs.258687 · Cited by 36
Failure of lysosomal acidification and endomembrane network in neurodegeneration
Kim, S.-H., Cho, Y.-S., & Jung, Y. (2025) · Experimental & Molecular Medicine · doi:10.1038/s12276-025-01579-x · Cited by 32
Cerebrovascular Changes and Neurodegeneration Related to Hyperlipidemia: Characteristics of the Human ApoB-100 Transgenic Mice
Tóth, M. E., Dukay, B., Hoyk, Z., & Sántha, M. (2020) · Current Pharmaceutical Design · doi:10.2174/1381612826666200218101818 · Cited by 32
The interplay between aging‐associated loss of protein homeostasis and extracellular vesicles in neurodegeneration
Guix, F. X. (2019) · Journal of Neuroscience Research · doi:10.1002/jnr.24526 · Cited by 30
Sphingosine kinase 2 potentiates amyloid deposition but protects against hippocampal volume loss and demyelination in a mouse model of Alzheimer’s disease
Lei, M., Teo, J. D., Song, H., McEwen, H. P., Yup Lee, J., Couttas, T. A., Duncan, T., Chesworth, R., Bertz, J., Przybyla, M., et al. (2019) · The Journal of Neuroscience · doi:10.1523/jneurosci.0524-19.2019 · Cited by 27
Endosomal Trafficking in Alzheimer's Disease, Parkinson's Disease, and Neuronal Ceroid Lipofuscinosis
Qureshi, Y. H., Baez, P., & Reitz, C. (2020) · Molecular and Cellular Biology · doi:10.1128/mcb.00262-20 · Cited by 25
Fats, Friends or Foes: Investigating the Role of Short- and Medium-Chain Fatty Acids in Alzheimer’s Disease
Ameen, A. O., Freude, K., & Aldana, B. I. (2022) · Biomedicines · doi:10.3390/biomedicines10112778 · Cited by 29
ApoE4 expression disrupts tau uptake, trafficking, and clearance in astrocytes
Eisenbaum, M., Pearson, A., Ortiz, C., Mullan, M., Crawford, F., Ojo, J., & Bachmeier, C. (2024) · Glia · doi:10.1002/glia.24469 · Cited by 25
Protective ApoE variants support neuronal function by effluxing oxidized phospholipids
Ralhan, I., Do, A. D., Bae, J.-Y., Feringa, F. M., Cai, W., Chang, J., Chik, K., Lee, N. Y. J., Gerry, C. J., van der Kant, R., et al. (2026) · Neuron · doi:10.1016/j.neuron.2025.10.040 · Cited by 23
Predictability of polygenic risk score for progression to dementia and its interaction with APOE ε4 in mild cognitive impairment
Pyun, J., Park, Y. H., Lee, K., Kim, S., Saykin, A. J., Nho, K. T., & Initiative, A. D. N. (2021) · Translational Neurodegeneration · doi:10.1186/s40035-021-00259-w · Cited by 26
Cell type-specific functions of Alzheimer's disease endocytic risk genes
Maninger, J.-K., Nowak, K., Goberdhan, S., O'Donoghue, R., & Connor-Robson, N. (2024) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2022.0378 · Cited by 22
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
Apolipoprotein E4–driven effects on inflammatory and neurotrophic factors in peripheral extracellular vesicles from cognitively impaired, no dementia participants who converted to Alzheimer's disease
Khedher, M. R. B., Haddad, M., Laurin, D., & Ramassamy, C. (2021) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1002/trc2.12124 · Cited by 21
Microglial replacement in a Sandhoff disease mouse model reveals myeloid-derived β-hexosaminidase is necessary for neuronal health
Tsourmas, K. I., Butler, C. A., Kwang, N. E., Sloane, Z. R., Dykman, K. J. G., Maloof, G. O., Choudhury, B., Paulchakrabarti, M., Prekopa, C. A., Tabaie, E. Z., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-63237-0 · Cited by 25
Lysosomal proteomics reveals mechanisms of neuronal APOE4-associated lysosomal dysfunction
Krogsaeter, E., McKetney, J., Valiente‐Banuet, L., Marquez, A., Willis, A., Cakir, Z., Stevenson, E. J., Jang, G. Μ., Rao, A. T., Li, E., et al. (2025) · Autophagy · doi:10.1080/15548627.2025.2576613 · Cited by 22
Impact of endolysosomal dysfunction upon exosomes in neurodegenerative diseases
Izco, M., Carlos, E., & Alvarez‐Erviti, L. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105651 · Cited by 18
Exploring the potential role of rab5 protein in endo-lysosomal impairment in Alzheimer’s disease
Behl, T., Kaur, D., Sehgal, A., Singh, S., Makeen, H. A., Albratty, M., Abdellatif, A. A. H., Dachani, S. R., & BUNGAU, S. G. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.112773 · Cited by 20
A Review of ApoE4 Interference Targeting Mitophagy Molecular Pathways for Alzheimer's Disease
Chen, H., Chen, F., Jiang, Y., Zhang, L., Hu, G., Sun, F., Zhang, M., Ji, Y., Chen, Y., Che, G., et al. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.881239 · Cited by 19
The “Cerebrospinal Fluid Sink Therapeutic Strategy” in Alzheimer’s Disease—From Theory to Design of Applied Systems
Schreiner, T. G., Menéndez‐González, M., & Popescu, B. O. (2022) · Biomedicines · doi:10.3390/biomedicines10071509 · Cited by 18
Modifications of the endosomal compartment in fibroblasts from sporadic Alzheimer’s disease patients are associated with cognitive impairment
Xicota, L., Lagarde, J., Eysert, F., Grenier-Boley, B., Rivals, I., Botté, A., Forlani, S., Landron, S., Gautier, C., Gabriel, C., et al. (2023) · Translational Psychiatry · doi:10.1038/s41398-023-02355-z · Cited by 15
Defective Lysosomal Lipid Catabolism as a Common Pathogenic Mechanism for Dementia
Lee, J. Y., Marian, O. C., & Don, A. S. (2021) · NeuroMolecular Medicine · doi:10.1007/s12017-021-08644-4 · Cited by 18
Altered expression of Presenilin2 impacts endolysosomal homeostasis and synapse function in Alzheimer’s disease-relevant brain circuits
Perdok, A., Acker, Z. P. V., Vrancx, C., Sannerud, R., Vorsters, I., Verrengia, A., Callaerts‐Vegh, Z., Creemers, E., Fernández, S. G., D’hauw, B., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-54777-y · Cited by 18
A Review of APOE Genotype-Dependent Autophagic Flux Regulation in Alzheimer’s Disease
Chen, H., Chen, F., Zhang, M., Chen, Y., Cui, L., & Liang, C. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-210602 · Cited by 15
Apolipoprotein ε in Brain and Retinal Neurodegenerative Diseases
Abyadeh, M., Gupta, V., Paulo, J. A., Sheriff, S., Shadfar, S., Fitzhenry, M. J., Amirkhani, A., Gupta, V. B., Salekdeh, G. H., Haynes, P. A., et al. (2023) · Aging and Disease · doi:10.14336/ad.2023.0312-1 · Cited by 15
Cerebrospinal fluid exploratory proteomics and ketamine metabolite pharmacokinetics in human volunteers after ketamine infusion
Moaddel, R., Farmer, C., Yavi, M., Kadriu, B., Zhu, M., Fan, J., Chen, Q., Lehrmann, E., Fantoni, G., De, S., et al. (2023) · iScience · doi:10.1016/j.isci.2023.108527 · Cited by 14
Apolipoprotein E intersects with amyloid-β within neurons
Konings, S. C., Nyberg, E., Martinsson, I., Torres-Garcia, L., Klementieva, O. L., Almeida, C. G., & Gouras, G. K. (2023) · Life Science Alliance · doi:10.26508/lsa.202201887 · Cited by 12
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
Dr. Jekyll and Mr. Hyde: ApoE explains opposing effects of neuronal LRP1
Strickland, M. R., & Holtzman, D. M. (2019) · Journal of Clinical Investigation · doi:10.1172/jci127578 · Cited by 13
Cocaine Modulates the Neuronal Endosomal System and Extracellular Vesicles in a Sex-Dependent Manner
Barreto, B. R., D’Acunzo, P., Ungania, J. M., Das, S., Hashim, A., Goulbourne, C. N., Canals‐Baker, S., Saito, M., Saito, M., Sershen, H. W., et al. (2022) · Neurochemical Research · doi:10.1007/s11064-022-03612-1 · Cited by 12
Self-citation
Endosomal egress and intercellular transmission of hepatic ApoE-containing lipoproteins and its exploitation by the hepatitis C virus
Pham, M.-T., Lee, J., Ritter, C., Thielemann, R., Meyer, J., Haselmann, U., Funaya, C., Laketa, V., Rohr, K., & Bartenschlager, R. F. W. (2023) · PLoS Pathogens · doi:10.1371/journal.ppat.1011052 · Cited by 12
Development of AD-Like Pathology in Skeletal Muscle
Chen, X., Miller, N. M., Afghah, Z., & Geiger, J. D. (2019) · Journal of Parkinson’s Disease and Alzheimer’s Disease · doi:10.13188/2376-922x.1000028 · Cited by 10
Apolipoprotein E4 Effects a Distinct Transcriptomic Profile and Dendritic Arbor Characteristics in Hippocampal Neurons Cultured in vitro
Diaz, J. R., Martá-Ariza, M., Khodadadi‐Jamayran, A., Heguy, A., Tsirigos, A., Pankiewicz, J. E., Sullivan, P. M., & Sadowski, M. J. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.845291 · Cited by 11
Lewy body dementia: exploring biomarkers and pathogenic interactions of amyloid β, tau, and α-synuclein
Liang, J., Li, R., Wong, G., & Huang, X. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00879-0 · Cited by 13
Genomic Characterization of Host Factors Related to SARS-CoV-2 Infection in People with Dementia and Control Populations: The GR@ACE/DEGESCO Study
de Rojas, I., Hernández, I., Montrreal, L., Quintela, I., Calero, M., Royo, J. L., Vilas, R. H., González-Pérez, A., Macías, E. F., Macı́as, J., et al. (2021) · Journal of Personalized Medicine · doi:10.3390/jpm11121318 · Cited by 9
The Contributions of the Endolysosomal Compartment and Autophagy to APOE ɛ4 Allele-Mediated Increase in Alzheimer’s Disease Risk
Asiamah, E. A., Feng, B., Guo, R., Yaxing, X., Du, X., Liu, X., Zhang, J., Cui, H., & Ma, J. (2024) · Journal of Alzheimer s Disease · doi:10.3233/jad-230658 · Cited by 8
Elucidating the Role of Apolipoprotein E Isoforms in Spinal Cord Injury-Associated Neuropathology
Toro, C. A., Das, D. K., Cai, D., & Cardozo, C. P. (2019) · Journal of Neurotrauma · doi:10.1089/neu.2018.6334 · Cited by 8
APOE2, E3 and E4 differentially modulate cellular homeostasis, cholesterol metabolism and inflammatory response in isogenic iPSC-derived astrocytesPreprint
de Leeuw, S. M., Kirschner, A. W. T., Lindner, K., Rust, R., Wolski, W., Gavin, A., Nitsch, R. M., & Tackenberg, C. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.07.17.452644 · Cited by 8
Temporal Characterization of the Amyloidogenic APPswe/PS1dE9;hAPOE4 Mouse Model of Alzheimer’s Disease
Grenon, M. B., Papavergi, M.-T., Bathini, P., Sadowski, M. J., & Lemere, C. A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25115754 · Cited by 7
Cellular senescence induced by cholesterol accumulation is mediated by lysosomal ABCA1 in APOE4 and ADPreprint
Wang, S., Li, B., Cai, Z., Hugo, C., Li, J., Sun, Y. E., Lü, Q., Remaley, A. T., Julia, T. C. W., Chui, H. C., et al. (2024) · Research Square · doi:10.21203/rs.3.rs-4373201/v1 · Cited by 7
Quantitative and Kinetic Proteomics Reveal ApoE Isoform-dependent Proteostasis Adaptations in Mouse Brain
Zuniga, N. R., Earls, N. E., Denos, A. E. A., Elison, J. M., Jones, B. S., Smith, E. G., Moran, N. G., Broce, K. L., Romero, G. M., Hyer, C. D., et al. (2024) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1012407 · Cited by 9
Altered lipid metabolic homeostasis in the pathogenesis of Alzheimer’s disease
Marian, O. C., Tran, C., & Don, A. S. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-819404-1.00023-3 · Cited by 5
Protective ApoE variants support neuronal function by extracting peroxidated lipids
Ralhan, I., Do, A. D., Bae, J.-Y., Feringa, F. M., Cai, W., Chang, J., Chik, K., Lee, N. Y., Gerry, C., van der Kant, R., et al. (2025) · bioRxiv · doi:10.1101/2025.03.05.641722 · Cited by 4
ApoE4 disrupts intracellular trafficking and iron homeostasis in a reproducible iPSC-based model of human brain endothelial cells
Bell, L., Clerkin, S., Rizalar, F. S., Rizkallah, A., Stokar‐Regenscheit, N., Spijkers, X. M., Wevers, N. R., Simonneau, C., Augustin, A., Höllbacher, B., et al. (2025) · Stem Cell Reports · doi:10.1016/j.stemcr.2025.102607 · Cited by 7
Apolipoprotein E2 Expression Alters Endosomal Pathways in a Mouse Model With Increased Brain Exosome Levels During Aging
Peng, K. Y., Liemisa, B., Pasato, J., D’Acunzo, P., Pawlik, M., Heguy, A., Penikalapati, S. C., Labuza, A., Pidikiti, H., Alldred, M. J., et al. (2024) · Traffic · doi:10.1111/tra.12937 · Cited by 4
Self-citation
Cell-type-specific regulation of APOE levels in human neurons by the Alzheimer’s disease risk gene SORL1Preprint
Lee, H., Aylward, A. J., Pearse, R. V., Hsieh, Y., Augur, Z. M., Benoit, C. R., Chou, V., Knupp, A., Pan, C., Goberdhan, S., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.02.25.530017 · Cited by 4

Authors: Nuriel, T., Peng, K. Y., Ashok, A., Dillman, A. A., Figueroa, H. Y., Apuzzo, J., Ambat, J., Levy, E., Cookson, M. R., Mathews, P. M., & Duff, K. E.
Affiliations: Columbia University Irving Medical Center (US)
NYU Langone Health (US)
National Institutes of Health (US)
Nathan Kline Institute for Psychiatric Research (US)
Corresponding author: Mathews, Paul M.
Duff, Karen E.
ORCID: Nuriel, Tal
Peng, Katherine Y.
Ashok, Archana
Dillman, Allissa A.
Levy, Efrat
Mathews, Paul M.
Duff, Karen E.
Venue: Frontiers in Neuroscience
Publisher: Frontiers Media SA
Published: 2017-12-12
Volume: 11
Pages: 702-702
ISSN: 1662-453X (ISSN-L)
DOI: 10.3389/fnins.2017.00702
PMC: PMC5733017
OpenAlex: W2775642640
Cited by: 140
References: 59
Citations by year: 2026: 10 · 2025: 17 · 2024: 16 · 2023: 15 · 2022: 19 · 2021: 21 · 2020: 23 · 2019: 17 · 2018: 2
FWCI: 8.50
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
Locations: Frontiers in Neuroscience (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: National Institute on Aging (AG048408, AG047797, AG017617)
National Institute of Neurological Disorders and Stroke (NS071836)
BrightFocus Foundation (A2014200F)
Cure Alzheimer's Fund
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
Keywords: APOE ε4, apolipoprotein E, endolysosomal pathway, Alzheimer's disease, late-onset Alzheimer's disease, early endosomes, lysosomal dysfunction, genetic risk factors, transcriptomics

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

The endosomal-lysosomal pathway is dysregulated by APOE4 expression in vivo

Abstract

Overview

Integrity signals

Figures

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks