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

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.

doi:10.3389/fnins.2017.00702

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

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 +3 more·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

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?

APOE4-bound cholesterol, taken up by the cell, is released from the receptor in the late endosome or lysosome, and aggregation of APOE4 has been shown to cause endosomal congestion and dysfunction.
“APOE4-bound cholesterol, taken up by the cell, is released from the receptor in the late endosome or lysosome, and aggregation of APOE4 has been shown to cause endosomal congestion and dysfunction (Narayan et al., 2020; Nuriel et al., 2017; Rawat et al., 2019).”
From APOE2, E3, and E4 differentially modulate cellular homeostasis, cholesterol metabolism, and inflammatory response in isogenic iPSC-derived astrocytes (2022) · cites this paper as Nuriel et al., 2017
The Discussion reports that APOE4 expression causes endosomal–lysosomal dysregulation and enlarged early endosomes in aged mice. It does not show that APOE4 aggregation causes this dysfunction, or describe receptor release of APOE4-bound cholesterol in late endosomes or lysosomes. The Introduction discusses aggregation of Aβ, not aggregation of APOE4. (LLM, conf=0.87)
Experimental — accuracy not yet measured
The endosomal-lysosomal dysregulation observed in the brains of aged APOE4 mice was not restricted to the EC.
“As the endosomal-lysosomal dysregulation that we observed in the brains of aged APOE4 mice was not restricted to the EC30”
From APOE4 is Associated with Differential Regional Vulnerability to Bioenergetic Deficits in Aged APOE Mice (2020) · cites this paper as [30]
APOE4 affects the endosomal-lysosomal pathway and the APOE4 induced recycling block can be rescued by decreasing pH.
“APOE4 affects, however, the endosomal-lysosomal pathway (Nuriel et al, 2017) and the APOE4 induced recycling block can be rescued by decreasing pH (Xian et al, 2018).”
From APOE from astrocytes restores Alzheimer’s Aβ-pathology and DAM-like responses in APOE deficient microglia (2024) · cites this paper as Nuriel et al, 2017

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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 1,227 · cited 2× · see citing works
“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 · see citing works
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 · see citing works
Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia
Reiman, E. M., Chen, K., Alexander, G. E., Caselli, R. J., Bandy, D., Osborne, D., Saunders, A. M., & Hardy, J. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2635903100 · Cited by 977 · see citing works
Apolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer's disease
Holtzman, D. M., Bales, K. R., Tenkova, T., Fagan, A. M., Parsadanian, M., Sartorius, L. J., Mackey, B., Olney, J., McKeel, D., Wozniak, D., et al. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.050004797 · Cited by 937 · see citing works
Amyloid-associated proteins α1-antichymotrypsin and apolipoprotein E promote assembly of Alzheimer β-protein into filaments
Ma, J., Yee, A., Brewer, H. B., Das, S., & Potter, H. (1994) · Nature · doi:10.1038/372092a0 · Cited by 871 · see citing works
Lack of apolipoprotein E dramatically reduces amyloid β-peptide deposition
Bales, K. R., Verina, T., Dodel, R. C., Du, Y., Altstiel, L., Bender, M., Hyslop, P., Johnstone, E. M., Little, S. P., Cummins, D. J., et al. (1997) · Nature Genetics · doi:10.1038/ng1197-263 · Cited by 830 · see citing works
Endocytic pathway abnormalities precede amyloid beta deposition in sporadic Alzheimer's disease and Down syndrome: differential effects of APOE genotype and presenilin mutations.
Cataldo, A., Peterhoff, C., Troncoso, J., Gómez-Isla, T., Hyman, B., & Nixon, R. (2000) · American Journal of Pathology · doi:10.1016/s0002-9440(10)64538-5 · Cited by 789 · 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
Targeted Replacement of the Mouse Apolipoprotein E Gene with the Common Human APOE3 Allele Enhances Diet-induced Hypercholesterolemia and Atherosclerosis
Sullivan, P. M., Mezdour, H., Aratani, Y., Knouff, C., Najib, J., Reddick, R. L., Quarfordt, S. H., & Maeda, N. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.29.17972 · Cited by 575 · see citing works
Declining brain activity in cognitively normal apolipoprotein E ɛ4 heterozygotes: A foundation for using positron emission tomography to efficiently test treatments to prevent Alzheimer's disease
Reiman, E. M., Caselli, R. J., Chen, K., Alexander, G. E., Bandy, D., & Frost, J. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.061509598 · Cited by 467 · see citing works
Amyloid precursor protein and endosomal-lysosomal dysfunction in Alzheimer's disease: inseparable partners in a multifactorial disease
Nixon, R. A. (2017) · The FASEB Journal · doi:10.1096/fj.201700359 · Cited by 400 · cited 2× · see citing works
“…pathway in both the production of Aβ (see review by Thinakaran and Koo, 2008) and the clearance of pathogenic proteins (see review by Nixon, 2017), we believe that APOE4-associated endosomal–lysosomal system dysregulation may be an early instigator of AD pathogenesis among APOE4…”
Background
Gene expression and cellular content of cathepsin D in Alzheimer's disease brain: Evidence for early up-regulation of the endosomal-lysosomal system
Cataldo, A. M., Barnett, J. L., Berman, S. A., Li, J., Quarless, S., Bursztajn, S., Lippa, C., & Nixon, R. A. (1995) · Neuron · doi:10.1016/0896-6273(95)90324-0 · Cited by 379 · see citing works
Endosome function and dysfunction in Alzheimer's disease and other neurodegenerative diseases
Nixon, R. A. (2004) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2004.09.018 · Cited by 371 · see citing works
ApoE4 reduces glutamate receptor function and synaptic plasticity by selectively impairing ApoE receptor recycling
Chen, Y., Durakoglugil, M. S., Xian, X., & Herz, J. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0914984107 · Cited by 368 · see citing works
Aβ localization in abnormal endosomes: association with earliest Aβ elevations in AD and Down syndrome
Cataldo, A. M., Petanceska, S., Terio, N. B., Peterhoff, C. M., Durham, R., Mercken, M., Mehta, P. D., Buxbaum, J., Haroutunian, V., & Nixon, R. A. (2004) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2004.02.027 · Cited by 363 · see citing works
Recent Insights into the Structure, Regulation, and Function of the V-ATPases
Cotter, K., Stransky, L., McGuire, C., & Forgac, M. (2015) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2015.08.005 · Cited by 337 · see citing works
The Endosomal-Lysosomal System of Neurons in Alzheimer's Disease Pathogenesis: A Review
Nixon, R., Cataldo, A., & Mathews, P. (2000) · Neurochemical Research · doi:10.1023/a:1007675508413 · Cited by 332 · see citing works
Self-citation
Cortical morphology in children and adolescents with different apolipoprotein E gene polymorphisms: an observational study
Shaw, P., Lerch, J. P., Pruessner, J. C., Taylor, K. N., Rose, A. B., GREENSTEIN, D. K., CLASEN, L. S., Evans, A. C., Rapoport, J. L., & Giedd, J. N. (2007) · The Lancet Neurology · doi:10.1016/s1474-4422(07)70106-0 · Cited by 287 · see citing works
Apolipoprotein (apo) E4 enhances amyloid β peptide production in cultured neuronal cells: ApoE structure as a potential therapeutic target
Ye, S., Huang, Y., Müllendorff, K., Dong, L., Giedt, G., Meng, E. C., Cohen, F. E., Kuntz, I. D., Weisgraber, K. H., & Mahley, R. W. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0508693102 · Cited by 275 · see citing works
Fibrillogenesis in Alzheimer's disease of amyloid β peptides and apolipoprotein E
Castano, E. M., Prelli, F., Wisniewski, T., Golabek, A., Kumar, R. A., Soto, C., & Frangione, B. (1995) · Biochemical Journal · doi:10.1042/bj3060599 · Cited by 267 · see citing works
Microarray Analysis of Hippocampal CA1 Neurons Implicates Early Endosomal Dysfunction During Alzheimer's Disease Progression
Ginsberg, S. D., Alldred, M. J., Counts, S., Cataldo, A. M., Neve, R. L., Jiang, Y., Wuu, J., Chao, M. V., Mufson, E. J., Nixon, R. A., et al. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.05.030 · Cited by 257 · see citing works
AppGene Dosage Modulates Endosomal Abnormalities of Alzheimer's Disease in a Segmental Trisomy 16 Mouse Model of Down Syndrome
Cataldo, A. M., Petanceska, S., Peterhoff, C. M., Terio, N. B., Epstein, C. J., Villar, A., Carlson, E. J., Staufenbiel, M., & Nixon, R. A. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-17-06788.2003 · Cited by 241 · cited 2× · see citing works
“This magnitude of early endosome change is similar to that which was reported in Down syndrome mouse models (Cataldo et al., 2003), and is similar to the APOE4-dependent early endosomal alteration seen in human neurons in the prefrontal cortex in early-stage AD (Cataldo et al.”
Result
MRI of entorhinal cortex in mild Alzheimer's disease
Bobinski, M., de Leon, M. J., Convit, A. J., Santi, S. D., Węgiel, J., Tarshish, C. Y., Louis, L. A. S., & Wı́sniewski, H. M. (1999) · The Lancet · doi:10.1016/s0140-6736(05)74869-8 · Cited by 238 · see citing works
Apolipoprotein E and Alzheimer's disease: the influence of apolipoprotein E on amyloid-β and other amyloidogenic proteins
Huynh, T.-P. V., Davis, A. A., Ulrich, J. D., & Holtzman, D. M. (2017) · Journal of Lipid Research · doi:10.1194/jlr.r075481 · Cited by 210 · see citing works
Eukaryotic V-ATPase: Novel structural findings and functional insights
Marshansky, V. N., Rubinstein, J. L., & Grüber, G. (2014) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2014.01.018 · Cited by 196 · see citing works
Presenilins and Alzheimer disease
Broeckhoven, C. V. (1995) · Nature Genetics · doi:10.1038/ng1195-230 · Cited by 187 · see citing works
Apolipoprotein E4 Potentiates Amyloid β Peptide-induced Lysosomal Leakage and Apoptosis in Neuronal Cells
Ji, Z.-S., Miranda, R. D., Newhouse, Y. M., Weisgraber, K. H., Huang, Y., & Mahley, R. W. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m112109200 · Cited by 177 · see citing works
Differential Regulation of Amyloid-β Endocytic Trafficking and Lysosomal Degradation by Apolipoprotein E Isoforms
Li, J., Kanekiyo, T., Shinohara, M., Zhang, Y., LaDu, M. J., Xu, H., & Bu, G. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.420224 · Cited by 175 · see citing works
Aβ-independent roles of apolipoprotein E4 in the pathogenesis of Alzheimer's disease
Huang, Y. (2010) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2010.04.004 · Cited by 170 · see citing works
Reduced Posterior Cingulate Mitochondrial Activity in Expired Young Adult Carriers of the APOE ε4 Allele, the Major Late-Onset Alzheimer's Susceptibility Gene
Valla, J., Yaari, R., Wolf, A. B., Kusne, Y., Beach, T. G., Roher, A. E., Corneveaux, J. J., Huentelman, M. J., Caselli, R. J., & Reiman, E. M. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-100129 · Cited by 150 · see citing works
Impaired recycling of apolipoprotein E4 is associated with intracellular cholesterol accumulation
Heeren, J., Grewal, T., Laatsch, A., Becker, N., Rinninger, F., Rye, K.-A., & Beisiegel, U. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m409324200 · Cited by 139 · see citing works
Young APOE4 targeted replacement mice exhibit poor spatial learning and memory, with reduced dendritic spine density in the medial entorhinal cortexPreprint
Rodriguez, G. A., Burns, M. P., Weeber, E. J., & Rebeck, G. W. (2013) · Learning & Memory · doi:10.1101/lm.030031.112 · Cited by 134 · see citing works
Upregulation of select rab GTPases in cholinergic basal forebrain neurons in mild cognitive impairment and Alzheimer's disease
Ginsberg, S. D., Mufson, E. J., Alldred, M. J., Counts, S., Wuu, J., Nixon, R. A., & Che, S. (2011) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2011.05.012 · Cited by 133 · see citing works
Regional Selectivity of rab5 and rab7 Protein Upregulation in Mild Cognitive Impairment and Alzheimer's Disease
Ginsberg, S. D., Mufson, E. J., Counts, S., Wuu, J., Alldred, M. J., Nixon, R. A., & Che, S. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-101080 · Cited by 128 · see citing works
Effects of Age, Sex, and Ethnicity on the Association Between Apolipoprotein E Genotype and Alzheimer Disease: A Meta-analysis
Farrer, L. A. (1997) · JAMA · doi:10.1001/jama.1997.03550160069041 · Cited by 124 · cited 1× · see citing works
“Carriers of the ε4 allele of APOE are at a significantly increased risk of developing late-onset AD (Farrer et al., 1997).”
Background
Defective macroautophagic turnover of brain lipids in the TgCRND8 Alzheimer mouse model: prevention by correcting lysosomal proteolytic deficits
Yang, D.-S., Stavrides, P., Saito, M., Kumar, A., Rodriguez-Navarro, J. A., Pawlik, M., Huo, C., Walkley, S. U., Saito, M., Cuervo, A. M., et al. (2014) · Brain · doi:10.1093/brain/awu278 · Cited by 114 · 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
Inhibition of the canonical Wnt signaling pathway by apolipoprotein E4 in PC12 cells
Caruso, A., Motolese, M., Iacovelli, L., Caraci, F., Copani, A., Nicoletti, F., Terstappen, G. C., Gaviraghi, G., & Caricasole, A. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.03867.x · Cited by 101 · see citing works
Functional Genomics of Brain Aging and Alzheimers Disease: Focus on Selective Neuronal Vulnerability
Wang, X., Michaelis, M. L., & Michaelis, E. K. (2010) · Current Genomics · doi:10.2174/138920210793360943 · Cited by 93 · see citing works
Partial BACE1 Reduction in a Down Syndrome Mouse Model blocks Alzheimer-related Endosomal Anomalies and Cholinergic Neurodegeneration: Role of APP-CTF
Jiang, Y., Rigoglioso, A., Peterhoff, C., Pawlik, M., Sato, Y., Bleiwas, C., Stavrides, P. H., Smiley, J., Ginsberg, S. D., Mathews, P., et al. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2015.11.013 · Cited by 92 · see citing works
Self-citation
The role of apolipoprotein E in lipid metabolism in the central nervous system
Han, X.-L. (2004) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-004-4009-z · Cited by 70 · see citing works
Apolipoprotein E as a β-amyloid-independent factor in Alzheimer’s disease
Wolf, A. B., Valla, J., Bu, G., Kim, J., LaDu, M., Reiman, E. M., & Caselli, R. J. (2013) · Alzheimer's Research & Therapy · doi:10.1186/alzrt204 · Cited by 55 · see citing works
The endosomal trafficking of apolipoprotein E3 and E4 in cultured human brain neurons and astrocytes.
Dekroon, R., & Armati, P. (2001) · Neurobiology of Disease · doi:10.1006/nbdi.2000.0362 · Cited by 39 · see citing works
Early Endosomal Abnormalities and Cholinergic Neuron Degeneration in Amyloid-β Protein Precursor Transgenic Mice
Choi, J. H. K., Kaur, G., Mazzella, M. J., Morales‐Corraliza, J., Levy, E., & Mathews, P. M. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-122143 · Cited by 38 · see citing works
Self-citation
Initial results of a genome survey for novel alzheimer's disease risk genes: association with a locus on the X chromosome
Zubenko, G. S., Stiffler, J. S., Hughes, H. B., Hurtt, M. R., & Kaplan, B. B. (1998) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(19980207)81:1 · Cited by 29 · see citing works
Recycling of apolipoprotein E is not associated with cholesterol efflux in neuronal cells.
Rellin, L., Heeren, J., & Beisiegel, U. (2008) · Biochimica et Biophysica Acta · doi:10.1016/j.bbalip.2008.02.001 · Cited by 24 · see citing works
Untitled work
(2002) · PubMed · Cited by 24 · see citing works
Two Alzheimer’s disease risk genes increase entorhinal cortex volume in young adults
DiBattista, A. M., Stevens, B. W., Rebeck, G. W., & Green, A. E. (2014) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2014.00779 · Cited by 22 · see citing works
Post-Translational Decrease in Respiratory Chain Proteins in the Polg Mutator Mouse Brain
Hauser, D. N., Dillman, A., Ding, J., Li, Y., & Cookson, M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0094646 · Cited by 13 · see citing works
Self-citation
Alzheimer GeneAPOEε4 Linked to Brain Development in Infants
Donald, J. M. M., & Krainc, D. (2014) · JAMA · doi:10.1001/jama.2013.285400 · Cited by 10 · see citing works
ADAR2 affects mRNA coding sequence edits with only modest effects on gene expression or splicingin vivo
Dillman, A., Cookson, M., & Galter, D. (2015) · RNA Biology · doi:10.1080/15476286.2015.1110675 · Cited by 8 · see citing works
Self-citation

Flagged first, then by citations

Research works printed but not linked: 1

Houlden H. Crook R. Backhovens H. Prihar G. Baker M. Hutton M.. (1998). ApoE genotype is a risk factor in nonpresenilin early-onset Alzheimer's disease families. Am. J. Med. Genet. 81, 117– 121. 9514597

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 · see citing works
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 · see citing works
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 · 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
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 · see citing works
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 · 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
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 · 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
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 · see citing works
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 · see citing works
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 229 · see citing works
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 · 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
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 192 · see citing works
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 · see citing works
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
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 164 · see citing works
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 152 · see citing works
Self-citation
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · 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
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 · see citing works
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 · see citing works
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 80 · see citing works
Exosome Production Is Key to Neuronal Endosomal Pathway Integrity in Neurodegenerative Diseases
Mathews, P., & Levy, E. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.01347 · Cited by 73 · see citing works
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 · see citing works
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 69 · see citing works
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 · see citing works
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 67 · see citing works
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 63 · see citing works
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 · see citing works
“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 · see citing works
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 · see citing works
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., 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 53 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
NHE6 depletion corrects ApoE4-mediated synaptic impairments and reduces amyloid plaque load
Pohlkamp, T., Xian, X., Wong, C. H. Y., 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 44 · see citing works
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 · see citing works
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 44 · see citing works
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 46 · see citing works
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 · see citing works
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 48 · see citing works
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 · see citing works
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 39 · see citing works
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 41 · see citing works
Self-citation
Finding memo: versatile interactions of the VPS10p-Domain receptors in Alzheimer’s disease
Salašová, A., Monti, G., Andersen, O. M., & Nykjær, A. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00576-2 · Cited by 35 · see citing works
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 38 · see citing works
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 · see citing works
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 · 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
Isoform-dependent lysosomal degradation and internalization of apolipoprotein E requires autophagy proteins
Fote, G., Geller, N. R., Efstathiou, N. E., Hendricks, N. G., Vavvas, D. G., Reidling, J. C., Thompson, L. M., & Steffan, J. S. (2022) · Journal of Cell Science · doi:10.1242/jcs.258687 · Cited by 33 · see citing works
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 29 · see citing works
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 31 · see citing works
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 29 · see citing works
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 · see citing works
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 26 · see citing works
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 28 · see citing works
<scp>ApoE4</scp> 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 27 · see citing works
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 · see citing works
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 25 · see citing works
Cell type-specific functions of Alzheimer's disease endocytic risk genes
Maninger, J., 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 21 · see citing works
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 · see citing works
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 · see citing works
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 24 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 17 · see citing works
Defective Lysosomal Lipid Catabolism as a Common Pathogenic Mechanism for Dementia
Lee, J. Y., Marian, O. C., & Don, A. (2021) · Neuromolecular medicine · doi:10.1007/s12017-021-08644-4 · Cited by 13 · see citing works
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 17 · see citing works
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 · see citing works
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 14 · see citing works
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 · see citing works
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 · see citing works
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
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 · see citing works
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 · see citing works
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 10 · see citing works
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 · see citing works
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 10 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 6 · see citing works
Altered lipid metabolic homeostasis in the pathogenesis of Alzheimer’s disease
Marian, O. C., Tran, C. L., & Don, A. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-819404-1.00023-3 · Cited by 2 · see citing works
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 · see citing works
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 4 · see citing works
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 · see citing works
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 · see citing works

P3‐175: APOE4 INDUCES REGION‐SPECIFIC DYSFUNCTION IN THE ENTORHINAL CORTEX OF AGED APOE4 MICE
Arain, H. A., Figueroa, H. Y., Área-Gómez, E., Duff, K., & Nuriel, T. (2019) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2019.06.3204
Self-citation
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 · see citing works
Self-citation
Examining APOE4 overexpression effects in iAstrocytes across European and African ancestries
Dykxhoorn, D. M., Oron, O., Trittipo, J., Adams, L. D., Starks, T. D., Acosta, H., Feliciano‐Astacio, B. E., Byrd, G. S., Pericak‐Vance, M. A., Griswold, A. J., et al. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.092321
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 · see citing works
Self-citation
Signatures of disrupted synaptic maintenance in the entorhinal cortex of both pathology‐free APOE4 carriers and aged APOE4 mice
Arain, H. A., Kumar, G., Figueroa, H. Y., Cookson, M., Mathews, P. M., Duff, K., & Nuriel, T. (2020) · Alzheimer s & Dementia · doi:10.1002/alz.046192
Self-citation

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: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Health Sciences › Medicine › Epidemiology › 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

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks