Apolipoprotein E in Alzheimer's Disease: An Update

Yu, Jin-Tai; Tan, Lan; Hardy, John

doi:10.1146/annurev-neuro-071013-014300

Cited by 394Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

The DOI matches its Crossref record; 152 of the 152 references it cites were found in a registry or an index.

Apolipoprotein E in Alzheimer's Disease: An Update

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Yu, Jin-Tai, Tan, Lan, Hardy, John·2014·Annual Review of Neuroscience

DOI 10.1146/annurev-neuro-071013-014300

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Abstract

The vast majority of Alzheimer's disease (AD) cases are late onset (LOAD), which is genetically complex with heritability estimates up to 80%. Apolipoprotein E (APOE) has been irrefutably recognized as the major genetic risk factor, with semidominant inheritance, for LOAD. Although the mechanisms that underlie the pathogenic nature of APOE in AD are still not completely understood, emerging data suggest that APOE contributes to AD pathogenesis through both amyloid-β (Aβ)-dependent and Aβ-independent pathways. Given the central role for APOE in the modulation of AD pathogenesis, many therapeutic strategies have emerged, including converting APOE conformation, regulating APOE expression, mimicking APOE peptides, blocking the APOE/Aβ interaction, modulating APOE lipidation state, and gene therapy. Accumulating evidence also suggests the utility of APOE genotyping in AD diagnosis, risk assessment, prevention, and treatment response.

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ApoE isoforms encoded by various APOE alleles differentially influence the rate of soluble Aβ clearance from the brain interstitial space and formation of Aβ parenchymal plaques and VAβ.
“ApoE isoforms encoded by various APOE alleles differentially influence the rate of soluble Aβ clearance from the brain interstitial space and formation of Aβ parenchymal plaques and VAβ [32, 33].”
From APOE Genotype Differentially Modulates Effects of Anti-Aβ, Passive Immunization in APP Transgenic Mice (2017) · cites this paper as [33]
The sections on Aβ clearance and aggregation describe isoform-dependent clearance of soluble Aβ from interstitial fluid and differences in brain plaque deposition. The copy does not establish an isoform-dependent effect on VAβ formation specifically (searched: VAβ, vascular Aβ, cerebral amyloid angiopathy). (LLM, conf=0.84)
Experimental — accuracy not yet measured
The ɛ4 allele has detrimental effects on production, deposition, and clearance of amyloid-β, phosphorylation of tau, neurotoxicity, mitochondrial dysfunction, and blood-brain barrier permeability.
“The ɛ4 allele has detrimental effects on production, deposition, and clearance of amyloid-β, in phosphorylation of tau, in neurotoxicity, mitochondrial dysfunction, and in blood–brain barrier permeability.57,59,60”
From Plasma levels of apolipoprotein E, APOE genotype, and all-cause and cause-specific mortality in 105 949 individuals from a white general population cohort (2019) · cites this paper as [57]
The sections on Aβ aggregation and clearance, tau pathology, neurotoxicity, mitochondrial dysfunction, and blood–brain barrier permeability describe the adverse APOE4-related effects listed in the claim. The section on APP trafficking and Aβ production is more qualified: some cell-culture studies suggest APOE4 enhances Aβ production, but others found no clear isoform-specific effect, and the authors call for in vivo investigation. The claim presents that production effect as established. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Plausible mechanisms underlying the association between low apoE levels and dementia-associated mortality are not explained by peripheral lipid metabolism, but likely by the role of apoE in β-amyloid handling and in neurodegenerative processes.
“Plausible mechanisms underlying the association between low apoE levels and dementia-associated mortality are not explained by peripheral lipid metabolism, but likely by the role of apoE in β-amyloid handling and in neurodegenerative processes.57,58”
From Plasma levels of apolipoprotein E, APOE genotype, and all-cause and cause-specific mortality in 105 949 individuals from a white general population cohort (2019) · cites this paper as [57]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
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APOE genotype critically affects the burden of Aβ pathology in sporadic AD.
“APOE genotype critically affects the burden of Aβ pathology in sporadic AD.”
From APOE Genotype Differentially Modulates Effects of Anti-Aβ, Passive Immunization in APP Transgenic Mice (2017) · cites this paper as [33]

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Integrative genomics identifies APOE ε4 effectors in Alzheimer's disease
Rhinn, H., Fujita, R., Qiang, L., Cheng, R., Lee, J. H., & Abeliovich, A. (2013) · Nature · doi:10.1038/nature12415 · Cited by 151
Retracted
The diagnosis of dementia due to Alzheimer's disease: Recommendations from the National Institute on Aging‐Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease
McKhann, G. M., Knopman, D. S., Chertkow, H., Hyman, B. T., Jack, C. R., Kawas, C. H., Klunk, W. E., Koroshetz, W. J., Manly, J. J., Mayeux, R., et al. (2011) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.03.005 · Cited by 18,657
Gene Dose of Apolipoprotein E Type 4 Allele and the Risk of Alzheimer's Disease in Late Onset Families
Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., Roses, A. D., Haines, J. L., & Pericak-Vance, M. A. (1993) · Science · doi:10.1126/science.8346443 · Cited by 9,429
Meta-Analysis of 74,046 Individuals Identifies 11 New Susceptibility Loci for Alzheimer’s Disease
(EADI), E. A. D. I., Lambert, J.-C., (GERAD), G. A. E. R. I. A. D., Alzheimer's Disease Genetic Consortium (ADGC), (CHARGE), C. F. H. A. A. R. I. G. E., Ibrahim-Verbaas, C. A., Harold, D., Naj, A. C., Sims, R., Bellenguez, C., et al. (2013) · Nature Genetics · doi:10.1038/ng.2802 · Cited by 4,336
Self-citation
Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy
Liu, C.-C., Kanekiyo, T., Xu, H., & Bu, G. (2013) · Nature Reviews Neurology · doi:10.1038/nrneurol.2012.263 · Cited by 3,459
2013 Alzheimer's disease facts and figures
Thies, W. H., & Bleiler, L. (2013) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2013.02.003 · Cited by 3,365
TREM2 Variants in Alzheimer's Disease
Guerreiro, R., Wojtas, A., Bras, J., Carrasquillo, M., Rogaeva, E., Majounie, E., Cruchaga, C., Sassi, C., Kauwe, J. S. K., Younkin, S., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1211851 · Cited by 3,020
Self-citation
Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders
Zlokovic, B. V. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn3114 · Cited by 2,969
Variant of TREM2 Associated with the Risk of Alzheimer's Disease
Jonsson, T., Stefansson, H., Steinberg, S., Jonsdottir, I., Jonsson, P. V., Snaedal, J., Bjornsson, S., Huttenlocher, J., Levey, A. I., Lah, J. J., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1211103 · Cited by 2,558
Decreased Clearance of CNS β-Amyloid in Alzheimer’s Disease
Mawuenyega, K. G., Sigurdson, W., Ovod, V., Munsell, L., Kasten, T., Morris, J. C., Yarasheski, K. E., & Bateman, R. J. (2010) · Science · doi:10.1126/science.1197623 · Cited by 2,078
Vitamin E and Donepezil for the Treatment of Mild Cognitive Impairment
Petersen, R. C., Thomas, R. G., Grundman, M., Bennett, D., Doody, R., Ferris, S., Galasko, D., Jin, S., Kaye, J., Levey, A., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa050151 · Cited by 1,844
Role of Genes and Environments for Explaining Alzheimer Disease
Gatz, M., Reynolds, C. A., Fratiglioni, L., Johansson, B., Mortimer, J. A., Berg, S., Fiske, A., & Pedersen, N. L. (2006) · Archives of General Psychiatry · doi:10.1001/archpsyc.63.2.168 · Cited by 1,798
CNS synaptogenesis promoted by glia-derived cholesterol
Mauch, D. H., Nägler, K., Schumacher, S., Göritz, C., Müller, E.-C., Otto, A., & Pfrieger, F. W. (2001) · Science · doi:10.1126/science.294.5545.1354 · Cited by 1,711
The role of apolipoprotein E in Alzheimer's disease
Kim, J., Basak, J. M., & Holtzman, D. M. (2009) · Neuron · doi:10.1016/j.neuron.2009.06.026 · Cited by 1,661
Effect of Physical Activity on Cognitive Function in Older Adults at Risk for Alzheimer Disease: A Randomized Trial
Lautenschlager, N. T., Cox, K. L., Flicker, L., Foster, J. K., van Bockxmeer, F. M., Xiao, J., Greenop, K. R., & Almeida, O. P. (2008) · JAMA · doi:10.1001/jama.300.9.1027 · Cited by 1,637
Distinct patterns of brain activity in young carriers of the APOE -ε4 allele
Filippini, N., MacIntosh, B. J., Hough, M. G., Goodwin, G. M., Frisoni, G. B., Smith, S. M., Matthews, P. M., Beckmann, C. F., & Mackay, C. E. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0811879106 · Cited by 1,613
Apolipoprotein E controls cerebrovascular integrity via cyclophilin A
Bell, R. D., Winkler, E. A., Singh, I., Sagare, A. P., Deane, R., Wu, Z., Holtzman, D. M., Betsholtz, C., Armulik, A., Sallstrom, J., et al. (2012) · Nature · doi:10.1038/nature11087 · Cited by 1,293 · cited 6×
“…various APOE isoforms differently modulate the components of the innate immune system via multiple signaling pathways, including NF-κB signaling (Bell et al. 2012), p38 MAP kinase signaling (Baitsch et al. 2011), JNK signaling (Pocivavsek et al. 2009), and endoplasmic reticulum stress…”
BackgroundInfluential
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×
“Several studies have reported human APOE isoform-dependent differences in Aβ deposition (APOE4 APOE3>APOE2) (Figure 2b) (Bales et al. 2009, Castellano et al. 2011, Youmans et al. 2012).”
Background
Nonsteroidal Antiinflammatory Drugs and the Risk of Alzheimer's Disease
in 't Veld, B. A., Ruitenberg, A., Hofman, A., Launer, L. J., van Duijn, C. M., Stijnen, T., Breteler, M. M. B., & Stricker, B. H. C. (2001) · New England Journal of Medicine · doi:10.1056/nejmoa010178 · Cited by 1,196 · cited 1×
“Additionally, several epidemiological and prospective studies suggest that long-term use of NSAIDs was associated with a significantly lower risk of AD in APOE ε4 subjects (in ‘t Veld et al. 2001, Szekely et al. 2008).”
Background
CSF Biomarkers and Incipient Alzheimer Disease in Patients With Mild Cognitive Impairment
Mattsson, N. (2009) · JAMA · doi:10.1001/jama.2009.1064 · Cited by 1,176
Apolipoprotein E and its receptors in Alzheimer's disease: pathways, pathogenesis and therapy
Bu, G. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2620 · Cited by 1,168
ApoE-Directed Therapeutics Rapidly Clear β-Amyloid and Reverse Deficits in AD Mouse Models
Cramer, P. E., Cirrito, J. R., Wesson, D. W., Lee, C. Y. D., Karlo, J. C., Zinn, A. E., Casali, B. T., Restivo, J. L., Goebel, W. D., James, M. J., et al. (2012) · Science · doi:10.1126/science.1217697 · Cited by 1,050
Linking lipids to Alzheimer's disease: cholesterol and beyond
Di Paolo, G., & Kim, T.-W. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn3012 · Cited by 972
ApoE Promotes the Proteolytic Degradation of Aβ
Jiang, Q., Lee, C. Y. D., Mandrekar, S., Wilkinson, B., Cramer, P., Zelcer, N., Mann, K., Lamb, B., Willson, T. M., Collins, J. L., et al. (2008) · Neuron · doi:10.1016/j.neuron.2008.04.010 · Cited by 876
Longitudinal assessment of Aβ and cognition in aging and Alzheimer disease
Villemagne, V. L., Pike, K. E., Chételat, G., Ellis, K. A., Mulligan, R. S., Bourgeat, P., Ackermann, U., Jones, G., Szoeke, C., Salvado, O., et al. (2011) · Annals of Neurology · doi:10.1002/ana.22248 · Cited by 833
APOE predicts amyloid‐beta but not tau Alzheimer pathology in cognitively normal aging
Morris, J. C., Roe, C. M., Xiong, C., Fagan, A. M., Goate, A. M., Holtzman, D. M., & Mintun, M. A. (2010) · Annals of Neurology · doi:10.1002/ana.21843 · Cited by 830
Fibrillar amyloid-β burden in cognitively normal people at 3 levels of genetic risk for Alzheimer's disease
Reiman, E. M., Chen, K., Liu, X., Bandy, D., Yu, M., Lee, W., Ayutyanont, N., Keppler, J., Reeder, S. A., Langbaum, J. B. S., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0900345106 · Cited by 785
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
A phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease
Salloway, S., Sperling, R., Gilman, S., Fox, N. C., Blennow, K., Raskind, M., Sabbagh, M., Honig, L. S., Doody, R., van Dyck, C. H., et al. (2009) · Neurology · doi:10.1212/wnl.0b013e3181c67808 · Cited by 753
APOE and Alzheimer disease: a major gene with semi-dominant inheritance
Genin, E., Hannequin, D., Wallon, D., Sleegers, K., Hiltunen, M., Combarros, O., Bullido, M. J., Engelborghs, S., De Deyn, P., Berr, C., et al. (2011) · Molecular Psychiatry · doi:10.1038/mp.2011.52 · Cited by 714
Efficacy of rosiglitazone in a genetically defined population with mild-to-moderate Alzheimer’s disease
Risner, M. E., Saunders, A. M., Altman, J. F. B., Ormandy, G. C., Craft, S., Foley, I. M., Zvartau-Hind, M. E., Hosford, D. A., Roses, A. D., & for the Rosiglitazone in Alzheimer's Disease Study Group (2006) · The Pharmacogenomics Journal · doi:10.1038/sj.tpj.6500369 · Cited by 686
Genetic evidence implicates the immune system and cholesterol metabolism in the aetiology of Alzheimer’s disease
Jones, L., Holmans, P. A., Hamshere, M. L., Harold, D., Moskvina, V., Ivanov, D., Pocklington, A., Abraham, R., Hollingworth, P., Sims, R., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0013950 · Cited by 606
Self-citation
Apolipoprotein E structure: insights into function
Hatters, D. M., Peters-Libeu, C. A., & Weisgraber, K. H. (2006) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2006.06.008 · Cited by 583
ApoE influences amyloid-β (Aβ) clearance despite minimal apoE/Aβ association in physiological conditions
Verghese, P. B., Castellano, J. M., Garai, K., Wang, Y., Jiang, H., Shah, A., Bu, G., Frieden, C., & Holtzman, D. M. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1220484110 · Cited by 556
Disclosure of APOE Genotype for Risk of Alzheimer's Disease
Green, R. C., Roberts, J. S., Cupples, L. A., Relkin, N. R., Whitehouse, P. J., Brown, T., Eckert, S. L., Butson, M., Sadovnick, A. D., Quaid, K. A., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0809578 · Cited by 554
Longitudinal Modeling of Age-Related Memory Decline and the APOE ε4 Effect
Caselli, R. J., Dueck, A. C., Osborne, D., Sabbagh, M. N., Connor, D. J., Ahern, G. L., Baxter, L. C., Rapcsak, S. Z., Shi, J., Woodruff, B. K., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0809437 · Cited by 528
Profile and Regulation of Apolipoprotein E (ApoE) Expression in the CNS in Mice with Targeting of Green Fluorescent Protein Gene to the ApoE Locus
Xu, Q., Bernardo, A., Walker, D., Kanegawa, T., Mahley, R. W., & Huang, Y. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.5476-05.2006 · Cited by 524
Amyloid-related imaging abnormalities in patients with Alzheimer's disease treated with bapineuzumab: a retrospective analysis
Sperling, R., Salloway, S., Brooks, D. J., Tampieri, D., Barakos, J., Fox, N. C., Raskind, M., Sabbagh, M., Honig, L. S., Porsteinsson, A. P., et al. (2012) · The Lancet Neurology · doi:10.1016/s1474-4422(12)70015-7 · Cited by 512
ABCA1 is required for normal central nervous system ApoE levels and for lipidation of astrocyte-secreted apoE
Wahrle, S. E., Jiang, H., Parsadanian, M., Legleiter, J., Han, X., Fryer, J. D., Kowalewski, T., & Holtzman, D. M. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m407963200 · Cited by 474
APOE4 Allele Disrupts Resting State fMRI Connectivity in the Absence of Amyloid Plaques or Decreased CSF Aβ42
Sheline, Y. I., Morris, J. C., Snyder, A. Z., Price, J. L., Yan, Z., D’Angelo, G., Liu, C., Dixit, S., Benzinger, T. L. S., Fagan, A. M., et al. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.3987-10.2010 · Cited by 444
Apolipoprotein E, ɛ4 allele as a major risk factor for sporadic early and late-onset forms of Alzheimer's disease: analysis of the 19q13.2 chromosomal region
Chartier‐Harlin, M., Parfitt, M., Legrain, S., Pérez‐Tur, J., Brousseau, T., Evans, A., Berr, C., Vldal, O., Roques, P. K., Gourlet, V., et al. (1994) · Human Molecular Genetics · doi:10.1093/hmg/3.4.569 · Cited by 437
Hypothesis: Microtubule Instability and Paired Helical Filament Formation in the Alzheimer Disease Brain Are Related to Apolipoprotein E Genotype
Strittmatter, W. J., Weisgraber, K. H., Goedert, M., Saunders, A. M., Huang, D., Corder, E. H., Dong, L., Jakes, R., Alberts, M. J., Gilbert, J. R., et al. (1994) · Experimental Neurology · doi:10.1006/exnr.1994.1019 · Cited by 433
Apolipoprotein e sets the stage: response to injury triggers neuropathology
Mahley, R. W., & Huang, Y. (2012) · Neuron · doi:10.1016/j.neuron.2012.11.020 · Cited by 412
Neuron-Specific Apolipoprotein E4 Proteolysis Is Associated with Increased Tau Phosphorylation in Brains of Transgenic Mice
Brecht, W. J., Harris, F. M., Chang, S., Tesseur, I., Yu, G.-Q., Xu, Q., Dee Fish, J., Wyss-Coray, T., Buttini, M., Mucke, L., et al. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.4315-03.2004 · Cited by 403
Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease
Wahrle, S. E., Jiang, H., Parsadanian, M., Kim, J., Li, A., Knoten, A., Jain, S., Hirsch-Reinshagen, V., Wellington, C. L., Bales, K. R., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci33622 · Cited by 370 · cited 1×
“Poorly lipidated APOE promotes amyloidogenesis in AD mouse models (Wahrle et al. 2005), whereas selective ABCA1 overexpression is sufficient to block amyloid plaque formation (Wahrle et al. 2008).”
Background
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
APOE genotype-specific differences in the innate immune response
Vitek, M. P., Brown, C. M., & Colton, C. A. (2009) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.11.014 · Cited by 362
Apolipoprotein E Induces Antiinflammatory Phenotype in Macrophages
Baitsch, D., Bock, H. H., Engel, T., Telgmann, R., Müller‐Tidow, C., Varga, G., Bot, M., Herz, J., Robenek, H., von Eckardstein, A., et al. (2011) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.111.222745 · Cited by 361
Mechanisms Underlying the Rapid Peroxisome Proliferator-Activated Receptor-γ-Mediated Amyloid Clearance and Reversal of Cognitive Deficits in a Murine Model of Alzheimer's Disease
Mandrekar-Colucci, S., Karlo, J. C., & Landreth, G. E. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.5268-11.2012 · Cited by 355 · cited 1×
“APOE4 carriers are consistently found with higher tau, phosphorylated tau, and tau/Aβ ratios at every disease stage (Mattsson et al. 2009, Vemuri et al. 2010).”
Background
Carboxyl-terminal-truncated apolipoprotein E4 causes Alzheimer's disease-like neurodegeneration and behavioral deficits in transgenic mice
Harris, F. M., Brecht, W. J., Xu, Q., Tesseur, I., Kekonius, L., Wyss-Coray, T., Fish, J. D., Masliah, E., Hopkins, P. C., Scearce-Levie, K., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1434398100 · Cited by 342
Apolipoprotein E4 effects in Alzheimer’s disease are mediated by synaptotoxic oligomeric amyloid-β
Koffie, R. M., Hashimoto, T., Tai, H.-C., Kay, K. R., Serrano-Pozo, A., Joyner, D., Hou, S., Kopeikina, K. J., Frosch, M. P., Lee, V. M., et al. (2012) · Brain · doi:10.1093/brain/aws127 · Cited by 327
Apolipoprotein E4 Causes Age- and Tau-Dependent Impairment of GABAergic Interneurons, Leading to Learning and Memory Deficits in Mice
Andrews-Zwilling, Y., Bien-Ly, N., Xu, Q., Li, G., Bernardo, A., Yoon, S. Y., Zwilling, D., Yan, T. X., Chen, L., & Huang, Y. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.4040-10.2010 · Cited by 326
Deletion of Abca1 Increases Aβ Deposition in the PDAPP Transgenic Mouse Model of Alzheimer Disease
Wahrle, S. E., Jiang, H., Parsadanian, M., Hartman, R. E., Bales, K. R., Paul, S. M., & Holtzman, D. M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m508780200 · Cited by 325
Apolipoprotein E: From lipid transport to neurobiology
Hauser, P. S., Narayanaswami, V., & Ryan, R. O. (2011) · Progress in Lipid Research · doi:10.1016/j.plipres.2010.09.001 · Cited by 320
Apolipoprotein E, Especially Apolipoprotein E4, Increases the Oligomerization of Amyloid β Peptide
Hashimoto, T., Serrano-Pozo, A., Hori, Y., Adams, K. W., Takeda, S., Banerji, A. O., Mitani, A., Joyner, D., Thyssen, D. H., Bacskai, B. J., et al. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.1542-12.2012 · Cited by 294 · cited 3×
“…via the blood-brain barrier (BBB) (Bachmeier et al. 2013, (c) Aβ clearance via enzymatic degradation ( Jiang et al. 2008); (d ) Aβ oligomerization (Hashimoto et al. 2012); and (e) Aβ clearance by drainage via the interstitial fluid (Castellano et al. 2011) or perivasculature (Hawkes et al.…”
BackgroundMethod
Genetic insights in Alzheimer's disease
Bettens, K., Sleegers, K., & Van Broeckhoven, C. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(12)70259-4 · Cited by 290
APOLIPOPROTEIN-E GENOTYPE AND ALZHEIMERS-DISEASE
Hardy, J., Houlden, H., Collinge, J., Kennedy, A. M., Newman, S., Rossor, M. N., Lannfelt, L., Lilius, L., Winblad, B. G., Crook, R., et al. (1993) · UCL Discovery (University College London) · Cited by 286
Self-citation
Apolipoprotein E genotype and Alzheimer's disease
Noguchi, S., Murakami, K., Yamada, N., Payami, H., Kaye, J. A., Heston, L. L., Bird, T. D., & Schellenberg, G. D. (1993) · The Lancet · doi:10.1016/0140-6736(93)91728-5 · Cited by 285
Topology of human apolipoprotein E3 uniquely regulates its diverse biological functions
Chen, J., Li, Q., & Wang, J. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1106420108 · Cited by 283
Apolipoprotein E Regulates the Integrity of Tight Junctions in an Isoform-dependent Manner in an in Vitro Blood-Brain Barrier Model
Nishitsuji, K., Hosono, T., Nakamura, T., Bu, G., & Michikawa, M. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.225532 · Cited by 275
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
Human APOE Isoform-Dependent Effects on Brain β-Amyloid Levels in PDAPP Transgenic Mice
Bales, K. R., Liu, F., Wu, S., Lin, S., Koger, D., DeLong, C., Hansen, J. C., Sullivan, P. M., & Paul, S. M. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.0887-09.2009 · Cited by 274
APOE4-specific Changes in Aβ Accumulation in a New Transgenic Mouse Model of Alzheimer Disease
Youmans, K. L., Tai, L. M., Nwabuisi-Heath, E., Jungbauer, L., Kanekiyo, T., Gan, M., Kim, J., Eimer, W. A., Estus, S., Rebeck, G. W., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.407957 · Cited by 268 · cited 2×
“Several studies have reported human APOE isoform-dependent differences in Aβ deposition (APOE4 APOE3>APOE2) (Figure 2b) (Bales et al. 2009, Castellano et al. 2011, Youmans et al. 2012).”
Background
Brain Differences in Infants at Differential Genetic Risk for Late-Onset Alzheimer Disease: A Cross-sectional Imaging Study
Dean, D. C., Jerskey, B. A., Chen, K., Protas, H., Thiyyagura, P., Roontiva, A., O'Muircheartaigh, J., Dirks, H., Waskiewicz, N., Lehman, K., et al. (2014) · JAMA Neurology · doi:10.1001/jamaneurol.2013.4544 · Cited by 263
Impaired insulin secretion increases the risk of Alzheimer disease
Rönnemaa, E., Zethelius, B., Sundelöf, J. E., Sundström, J., Degerman-Gunnarsson, M., Berne, C., Lannfelt, L., & Kilander, L. (2008) · Neurology · doi:10.1212/01.wnl.0000310646.32212.3a · Cited by 240
Hypometabolism and Altered Cerebrospinal Fluid Markers in Normal Apolipoprotein E E4 Carriers with Subjective Memory Complaints
Mosconi, L., De Santi, S., Brys, M., Tsui, W. H., Pirraglia, E., Glodzik-Sobanska, L., Rich, K. E., Switalski, R., Mehta, P. D., Pratico, D., et al. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.05.030 · Cited by 238
APOE genotype alters glial activation and loss of synaptic markers in mice
Zhu, Y., Nwabuisi‐Heath, E., Dumanis, S. B., Tai, L. M., Yu, C., Rebeck, G. W., & Ladu, M. J. (2012) · Glia · doi:10.1002/glia.22289 · Cited by 224
ApoE4 Decreases Spine Density and Dendritic Complexity in Cortical Neurons In Vivo
Dumanis, S. B., Tesoriero, J. A., Babus, L. W., Nguyen, M. T., Trotter, J. H., Ladu, M. J., Weeber, E. J., Turner, R. S., Xu, B., Rebeck, G. W., et al. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.4026-09.2009 · Cited by 220
Apolipoprotein E4 domain interaction mediates detrimental effects on mitochondria and is a potential therapeutic target for Alzheimer disease
Chen, H.-K., Ji, Z.-S., Dodson, S. E., Miranda, R. D., Rosenblum, C. I., Reynolds, I. J., Freedman, S. B., Weisgraber, K. H., Huang, Y., & Mahley, R. W. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.151084 · Cited by 209
Cross-Talk between Apolipoprotein E and Cytokines
Zhang, H., Wu, L., & Wu, J. (2011) · Mediators of Inflammation · doi:10.1155/2011/949072 · Cited by 208
Gene delivery of human apolipoprotein E alters brain Aβ burden in a mouse model of Alzheimer's disease
Dodart, J.-C., Marr, R. A., Koistinaho, M., Gregersen, B. M., Malkani, S., Verma, I. M., & Paul, S. M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409072102 · Cited by 207
Cerebrospinal fluid APOE levels: an endophenotype for genetic studies for Alzheimer's disease
Cruchaga, C., Kauwe, J. S. K., Nowotny, P., Bales, K., Pickering, E. H., Mayo, K., Bertelsen, S., Hinrichs, A., Fagan, A. M., Holtzman, D. M., et al. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds296 · Cited by 207
Haploinsufficiency of Human APOE Reduces Amyloid Deposition in a Mouse Model of Amyloid-β Amyloidosis
Kim, J., Jiang, H., Park, S., Eltorai, A. E. M., Stewart, F. R., Yoon, H., Basak, J. M., Finn, M. B., & Holtzman, D. M. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.3773-11.2011 · Cited by 204
NSAID use and dementia risk in the Cardiovascular Health Study*: Role of APOE and NSAID type
Szekely, C. A., Breitner, J. C. S., Fitzpatrick, A. L., Rea, T. D., Psaty, B. M., Kuller, L. H., & Zandi, P. P. (2008) · Neurology · doi:10.1212/01.wnl.0000284596.95156.48 · Cited by 204
APOE and BCHE as modulators of cerebral amyloid deposition: a florbetapir PET genome-wide association study
Ramanan, V. K., Risacher, S. L., Nho, K. T., Kim, S., Swaminathan, S., Shen, L., Foroud, T., Hakonarson, H. H., Huentelman, M. J., Aisen, P. S. S., et al. (2013) · Molecular Psychiatry · doi:10.1038/mp.2013.19 · Cited by 200
ATP-binding Cassette Transporter A1 Mediates the Beneficial Effects of the Liver X Receptor Agonist GW3965 on Object Recognition Memory and Amyloid Burden in Amyloid Precursor Protein/Presenilin 1 Mice*
Donkin, J. J., Stukas, S., Hirsch-Reinshagen, V., Namjoshi, D., Wilkinson, A., May, S., Chan, J., Fan, J., Collins, J., & Wellington, C. L. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.108100 · Cited by 200
A genome-wide scan for common variants affecting the rate of age-related cognitive decline
Jager, P. L. D., Shulman, J. M., Chibnik, L. B., Keenan, B. T., Raj, T., Wilson, R. S., Yu, L., Leurgans, S. E., Tran, D., Aubin, C., et al. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.09.033 · Cited by 196
Effect of apolipoprotein E on biomarkers of amyloid load and neuronal pathology in Alzheimer disease
Vemuri, P., Wiste, H. J., Weigand, S. D., Knopman, D. S., Shaw, L. M., Trojanowski, J. Q., Aisen, P. S., Weiner, M., Petersen, R. C., Jack, C. R., et al. (2010) · Annals of Neurology · doi:10.1002/ana.21953 · Cited by 195
Apolipoprotein Eε4 modifies Alzheimer's disease onset in an E280A PS1 kindred
Pastor, P., Roe, C. M., Villegas, A., Bedoya, G., Chakraverty, S., García, G., Tirado, V., Norton, J., Ríos, S., Martínez, M., et al. (2003) · Annals of Neurology · doi:10.1002/ana.10636 · Cited by 194
Low-density Lipoprotein Receptor Represents an Apolipoprotein E-independent Pathway of Aβ Uptake and Degradation by Astrocytes
Basak, J. M., Verghese, P. B., Yoon, H., Kim, J., & Holtzman, D. M. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.288746 · Cited by 192
Critical Role of Astroglial Apolipoprotein E and Liver X Receptor-α Expression for Microglial Aβ Phagocytosis
Terwel, D., Steffensen, K. R., Verghese, P. B., Kummer, M. P., Gustafsson, J.-Å., Holtzman, D. M., & Heneka, M. T. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.6546-10.2011 · Cited by 190
Rosiglitazone Induces Mitochondrial Biogenesis in Mouse Brain
Strum, J. C., Shehee, R., Virley, D. J., Richardson, J. C., Mattie, M. D., Selley, P., Ghosh, S., Nock, C. M., Saunders, A. M., & Roses, A. D. (2007) · Journal of Alzheimer s Disease · doi:10.3233/jad-2007-11108 · Cited by 183
Disruption of Arterial Perivascular Drainage of Amyloid-β from the Brains of Mice Expressing the Human APOE ε4 Allele
Hawkes, C. A., Sullivan, P. M., Hands, S. L., Weller, R. O., Nicoll, J. A. R., & Carare, R. O. (2012) · PLoS ONE · doi:10.1371/journal.pone.0041636 · Cited by 182
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 179
Apolipoprotein E promotes β-amyloid trafficking and degradation by modulating microglial cholesterol levels
Lee, C. Y. D., Tse, W., Smith, J. D., & Landreth, G. E. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.295451 · Cited by 178 · cited 2×
“F or p er so na l u se o nl y. degradation (Lee et al. 2012).”
Background
Reducing Human Apolipoprotein E Levels Attenuates Age-Dependent Aβ Accumulation in Mutant Human Amyloid Precursor Protein Transgenic Mice
Bien-Ly, N., Gillespie, A. K., Walker, D., Yoon, S. Y., & Huang, Y. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.0033-12.2012 · Cited by 170
Blocking the apolipoprotein E/amyloid-β interaction as a potential therapeutic approach for Alzheimer's disease
Sadowski, M. J., Pankiewicz, J., Scholtzova, H., Mehta, P. D., Prelli, F., Quartermain, D., & Wisniewski, T. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0604011103 · Cited by 167
Levels of Soluble Apolipoprotein E/Amyloid-β (Aβ) Complex Are Reduced and Oligomeric Aβ Increased with APOE4 and Alzheimer Disease in a Transgenic Mouse Model and Human Samples*
Tai, L. M., Bilousova, T., Jungbauer, L., Roeske, S. K., Youmans, K. L., Yu, C., Poon, W. W., Cornwell, L. B., Miller, C. A., Vinters, H. V., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.442103 · Cited by 165
Small Molecule Structure Correctors Abolish Detrimental Effects of Apolipoprotein E4 in Cultured Neurons
Chen, H.-K., Liu, Z., Meyer-Franke, A., Brodbeck, J., Miranda, R. D., McGuire, J. G., Pleiss, M. A., Ji, Z.-S., Balestra, M. E., Walker, D. W., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.276162 · Cited by 163
Posterior Cingulate Glucose Metabolism, Hippocampal Glucose Metabolism, and Hippocampal Volume in Cognitively Normal, Late-Middle-Aged Persons at 3 Levels of Genetic Risk for Alzheimer Disease
Protas, H. D., Chen, K., Langbaum, J. B. S., Fleisher, A. S., Alexander, G. E., Lee, W., Bandy, D., de Leon, M. J., Mosconi, L., Buckley, S., et al. (2013) · JAMA Neurology · doi:10.1001/2013.jamaneurol.286 · Cited by 161
Anti-apoE immunotherapy inhibits amyloid accumulation in a transgenic mouse model of Aβ amyloidosis
Kim, J., Eltorai, A. E. M., Jiang, H., Liao, F., Verghese, P. B., Kim, J., Stewart, F. R., Basak, J. M., & Holtzman, D. M. (2012) · Journal of Experimental Medicine · doi:10.1084/jem.20121274 · Cited by 160 · cited 1×
“3, inhibits amyloid accumulation in APPswe/PS1 E9 mice, suggesting antiapoE immunotherapy may represent a novel AD therapeutic strategy (Kim et al. 2012).”
Background
Understanding the association of apolipoprotein E4 with Alzheimer disease: clues from its structure
Zhong, N., & Weisgraber, K. H. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.r800009200 · Cited by 159
Comment on “ApoE-Directed Therapeutics Rapidly Clear β-Amyloid and Reverse Deficits in AD Mouse Models”
Fitz, N. F., Cronican, A. A., Lefterov, I., & Koldamova, R. (2013) · Science · doi:10.1126/science.1235809 · Cited by 151
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
Plasma apolipoprotein E and Alzheimer disease risk: The AIBL study of aging
Gupta, V. B., Laws, S. M., Villemagne, V. L., Ames, D., Bush, A. I., Ellis, K. A., Lui, J. K., Masters, C., Rowe, C. C., Szoeke, C., et al. (2011) · Neurology · doi:10.1212/wnl.0b013e318211c352 · Cited by 149
Comment on “ApoE-directed therapeutics rapidly clear β-amyloid and reverse deficits in AD mouse models.”
Price, A. R., Xu, G., Siemienski, Z. B., Smithson, L. A., Borchelt, D. R., Golde, T. E., & Felsenstein, K. M. (2013) · Science · doi:10.1126/science.1234089 · Cited by 138
Comment on “ApoE-Directed Therapeutics Rapidly Clear β-Amyloid and Reverse Deficits in AD Mouse Models”
Veeraraghavalu, K., Zhang, C., Miller, S., Hefendehl, J. K., Rajapaksha, T. W., Ulrich, J., Jucker, M., Holtzman, D. M., Tanzi, R. E., Vassar, R., et al. (2013) · Science · doi:10.1126/science.1235505 · Cited by 133
Structural differences between apoE3 and apoE4 may be useful in developing therapeutic agents for Alzheimer’s disease
Frieden, C., & Garai, K. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1207022109 · Cited by 133
Implication of apoE isoforms in cholesterol metabolism by primary rat hippocampal neurons and astrocytes.
Rapp, A., Gmeiner, B., & Hüttinger, M. (2006) · Biochimie · doi:10.1016/j.biochi.2005.10.007 · Cited by 130
Novel mechanism for defective receptor binding of apolipoprotein E2 in type III hyperlipoproteinemia
Dong, L., Parkin, S., Trakhanov, S. D., Rupp, B., Simmons, T., Arnold, K. S., Newhouse, Y. M., Innerarity, T. L., & Weisgraber, K. H. (1996) · Nature Structural & Molecular Biology · doi:10.1038/nsb0896-718 · Cited by 129
Cholesterol, APOE genotype, and Alzheimer disease: An epidemiologic study of Nigerian Yoruba
Hall, K., Murrell, J., Ogunniyi, A., Deeg, M., Baiyewu, O., Gao, S., Gureje, O., Dickens, J., Evans, R., Smith-Gamble, V., et al. (2006) · Neurology · doi:10.1212/01.wnl.0000194507.39504.17 · Cited by 128
Comment on “ApoE-Directed Therapeutics Rapidly Clear β-Amyloid and Reverse Deficits in AD Mouse Models”
Tesseur, I., Lo, A. C., Roberfroid, A., Dietvorst, S., Van Broeck, B., Borgers, M., Gijsen, H., Moechars, D., Mercken, M., Kemp, J., et al. (2013) · Science · doi:10.1126/science.1233937 · Cited by 128
Apolipoprotein E4 (1–272) fragment is associated with mitochondrial proteins and affects mitochondrial function in neuronal cells
Nakamura, T., Watanabe, A., Fujino, T., Hosono, T., & Michikawa, M. (2009) · Molecular Neurodegeneration · doi:10.1186/1750-1326-4-35 · Cited by 124
Accumulation of intraneuronal Aβ correlates with ApoE4 genotype
Christensen, D. Z., Schneider-Axmann, T., Lucassen, P. J., Bayer, T. A., & Wirths, O. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0666-1 · Cited by 120
The Pro-Neurotrophin Receptor Sortilin Is a Major Neuronal Apolipoprotein E Receptor for Catabolism of Amyloid-β Peptide in the Brain
Carlo, A.-S., Gustafsen, C., Mastrobuoni, G., Nielsen, M. S., Burgert, T., Hartl, D., Rohe, M., Nykjaer, A., Herz, J., Heeren, J., et al. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.2425-12.2013 · Cited by 117
Structure-dependent Impairment of Intracellular Apolipoprotein E4 Trafficking and Its Detrimental Effects Are Rescued by Small-molecule Structure Correctors
Brodbeck, J., McGuire, J., Liu, Z., Meyer-Franke, A., Balestra, M. E., Jeong, D.-E., Pleiss, M., McComas, C., Hess, F., Witter, D., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.217380 · Cited by 113
Differential effect of APOE genotype on amyloid load and glucose metabolism in AD dementia
Ossenkoppele, R., van der Flier, W. M., Zwan, M. D., Adriaanse, S. F., Boellaard, R., Windhorst, A. D., Barkhof, F., Lammertsma, A. A., Scheltens, P., & van Berckel, B. N. M. (2013) · Neurology · doi:10.1212/wnl.0b013e31827f0889 · Cited by 112
Dynamic Analysis of Amyloid β-Protein in Behaving Mice Reveals Opposing Changes in ISF versus Parenchymal Aβ during Age-Related Plaque Formation
Hong, S., Quintero-Monzon, O., Ostaszewski, B. L., Podlisny, D. R., Cavanaugh, W. T., Yang, T., Holtzman, D. M., Cirrito, J. R., & Selkoe, D. J. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.3272-11.2011 · Cited by 111
Apolipoprotein E isoforms and regulation of the innate immune response in brain of patients with Alzheimer's disease
Keene, C. D., Cudaback, E., Li, X., Montine, K. S., & Montine, T. J. (2011) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2011.08.002 · Cited by 103
The effect of apolipoprotein E (ApoE) genotype on biomarkers of amyloidogenesis, tau pathology and neurodegeneration in Alzheimer's disease
Leoni, V. (2011) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.2011.088 · Cited by 102
Apolipoprotein E4 Impairs Macrophage Efferocytosis and Potentiates Apoptosis by Accelerating Endoplasmic Reticulum Stress
Cash, J. G., Kuhel, D. G., Basford, J. E., Jaeschke, A., Chatterjee, T. K., Weintraub, N. L., & Hui, D. Y. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.377549 · Cited by 98
Low‐density lipoprotein receptors regulate microglial inflammation through c‐Jun N‐terminal kinase
Pocivavsek, A., Burns, M. P., & Rebeck, G. W. (2009) · Glia · doi:10.1002/glia.20772 · Cited by 96
The effect of acetyl-L-carnitine and R-α-lipoic acid treatment in ApoE4 mouse as a model of human Alzheimer's disease
Shenk, J. C., Liu, J., Fischbach, K., Xu, K., Puchowicz, M., Obrenovich, M. E., Gasimov, E. K., Morales, L., Ames, B. N., LaManna, J. C., et al. (2009) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2009.03.002 · Cited by 94
Blocking the Interaction between Apolipoprotein E and Aβ Reduces Intraneuronal Accumulation of Aβ and Inhibits Synaptic Degeneration
Kuszczyk, M. A., Sanchez, S., Pankiewicz, J., Kim, J., Duszczyk, M., Guridi, M., Asuni, A. A., Sullivan, P. M., Holtzman, D. M., & Sadowski, M. J. (2013) · The American Journal of Pathology · doi:10.1016/j.ajpath.2013.01.034 · Cited by 89 · cited 1×
“Loci identified by GWAS have much smaller effect sizes than that of APOE, typically with odds ratios between 1.1 and 1.3 in contrast to a ratio of ∼4 for APOE4 (Lambert et al. 2013).”
BackgroundInfluential
ApoE isoform-dependent changes in hippocampal synaptic function
Korwek, K. M., Trotter, J. H., LaDu, M. J., Sullivan, P. M., & Weeber, E. J. (2009) · Molecular Neurodegeneration · doi:10.1186/1750-1326-4-21 · Cited by 89
Apolipoprotein E modulates γ‐secretase cleavage of the amyloid precursor protein
Irizarry, M. C., Deng, A., Lleo, A., Berezovska, O., Von Arnim, C. A. F., Martin‐Rehrmann, M., Manelli, A., LaDu, M. J., Hyman, B. T., & Rebeck, G. W. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02581.x · Cited by 89
Distortion of Allelic Expression of Apolipoprotein E in Alzheimer's Disease
Lambert, J., Pérez‐Tur, J., Dupire, M., Galasko, D. R., Mann, D. M. A., Amouyel, P., Hardy, J., Delacourte, A., & Chartier‐Harlin, M. (1997) · Human Molecular Genetics · doi:10.1093/hmg/6.12.2151 · Cited by 86
Self-citation
APOE ε4 worsens hippocampal CA1 apical neuropil atrophy and episodic memory
Kerchner, G. A., Berdnik, D., Shen, J. C., Bernstein, J. D., Fenesy, M. C., Deutsch, G. K., Wyss-Coray, T., & Rutt, B. K. (2014) · Neurology · doi:10.1212/wnl.0000000000000154 · Cited by 86
APOE-Mimetic Peptides Reduce Behavioral Deficits, Plaques and Tangles in Alzheimer’s Disease Transgenics
Vitek, M. P., Christensen, D. J., Wilcock, D. M., Davis, J., Nostrand, W. E. V., Li, F. Q., & Colton, C. A. (2012) · Neurodegenerative Diseases · doi:10.1159/000334914 · Cited by 84
Omega-3 fatty acids and cognitive decline: modulation by ApoEε4 allele and depression
Samieri, C., Féart, C., Proust-Lima, C., Peuchant, E., Dartigues, J.-F., Amieva, H., & Barberger-Gateau, P. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.03.020 · Cited by 84
Presence of the APOE ε4 allele modifies the relationship between type 2 diabetes and cognitive performance: the Maine–Syracuse Study
Dore, G. A., Elias, M. F., Robbins, M. A., Elias, P. K., & Nagy, Z. (2009) · Diabetologia · doi:10.1007/s00125-009-1497-2 · Cited by 81
Response to Comments on “ApoE-Directed Therapeutics Rapidly Clear β-Amyloid and Reverse Deficits in AD Mouse Models”
Landreth, G. E., Cramer, P. E., Lakner, M. M., Cirrito, J. R., Wesson, D. W., Brunden, K. R., & Wilson, D. A. (2013) · Science · doi:10.1126/science.1234114 · Cited by 75
Apolipoprotein E3 (ApoE3) but Not ApoE4 Protects against Synaptic Loss through Increased Expression of Protein Kinase Cϵ
Sen, A., Alkon, D. L., & Nelson, T. J. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.312710 · Cited by 73
Apolipoprotein mimetic peptides: Mechanisms of action as anti-atherogenic agents
Osei-Hwedieh, D. O., Amar, M. J., Sviridov, D., & Remaley, A. T. (2010) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2010.12.003 · Cited by 71
The role of inflammatory processes in Alzheimer’s disease
Broussard, G. J., Mytar, J. O., Li, R., & Klapstein, G. J. (2012) · Inflammopharmacology · doi:10.1007/s10787-012-0130-z · Cited by 71
C-terminal-truncated apolipoprotein (apo) E4 inefficiently clears amyloid-β (Aβ) and acts in concert with Aβ to elicit neuronal and behavioral deficits in mice
Bien-Ly, N., Andrews-Zwilling, Y., Xu, Q., Bernardo, A., Wang, C., & Huang, Y. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1018381108 · Cited by 71
The Isoform-Specific Pathological Effects of ApoE4 in vivo are Prevented by a Fish Oil (DHA) Diet and are Modified by Cholesterol
Kariv-Inbal, Z., Yacobson, S., Berkecz, R., Péter, M., Janáky, T., Lütjohann, D., Broersen, L. M., Hartmann, T., & Michaelson, D. M. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-111265 · Cited by 70
Apolipoprotein E-Mimetics Inhibit Neurodegeneration and Restore Cognitive Functions in a Transgenic Drosophila Model of Alzheimer's Disease
Sarantseva, S. V., Timoshenko, S., Bolshakova, O. I., Karaseva, E., Rodin, D., Schwarzman, A. L., & Vitek, M. P. (2009) · PLoS ONE · doi:10.1371/journal.pone.0008191 · Cited by 70
Familial Alzheimer's disease: Site of mutation influences clinical phenotype
Lippa, C. F., Swearer, J. M., Kane, K., Nochlin, D., Bird, T. D., Ghetti, B. F., Nee, L. E., George‐Hyslop, P. S., Pollen, D. A., & Drachman, D. A. (2000) · Annals of Neurology · doi:10.1002/1531-8249(200009)48:3 · Cited by 67
Progressive loss of synaptic integrity in human apolipoprotein E4 targeted replacement mice and attenuation by apolipoprotein E2
Klein, R. C., Mace, B. E., Moore, S. D., & Sullivan, P. M. (2010) · Neuroscience · doi:10.1016/j.neuroscience.2010.10.027 · Cited by 67
Liver X receptor activation attenuates inflammatory response and protects cholinergic neurons in APP/PS1 transgenic mice
Cui, W., Sun, Y., Wang, Z., Xu, C., Peng, Y., & Li, R. (2012) · Neuroscience · doi:10.1016/j.neuroscience.2012.02.047 · Cited by 60
Plasma Signaling Proteins in Persons at Genetic Risk for Alzheimer Disease
Ringman, J. M., Elashoff, D. A., Geschwind, D. H., Welsh, B. T., Gylys, K. H., Lee, C., Cummings, J. L., & Cole, G. M. (2012) · Archives of Neurology · doi:10.1001/archneurol.2012.277 · Cited by 58
Apolipoprotein E level and cholesterol are associated with reduced synaptic amyloid beta in Alzheimer’s disease and apoE TR mouse cortex
Arold, S. P., Sullivan, P. M., Bilousova, T. V., Teng, E., Miller, C. A., Poon, W. W., Vinters, H. V., Cornwell, L. B., Saing, T., Cole, G. M., et al. (2011) · Acta Neuropathologica · doi:10.1007/s00401-011-0892-1 · Cited by 58
The Liver X Receptor Agonist GW3965 Improves Recovery from Mild Repetitive Traumatic Brain Injury in Mice Partly through Apolipoprotein E
Namjoshi, D., Martin, G., Donkin, J. J., Wilkinson, A., Stukas, S. K., Fan, J., Carr, M., Tabarestani, S., Wuerth, K. C., Hancock, R. E. W., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0053529 · Cited by 56
Molecular signatures in post-mortem brain tissue of younger individuals at high risk for Alzheimer's disease as based on APOE genotype
Conejero‐Goldberg, C., Hyde, T. M., Chen, S., Dreses‐Werringloer, U., Herman, M. M., Kleinman, J. E., Davies, P., & Goldberg, T. E. (2010) · Molecular Psychiatry · doi:10.1038/mp.2010.57 · Cited by 56
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Hara, M., Matsushima, T., Satoh, H., Iso-o, N., Noto, H., Togo, M., Kimura, S., Hashimoto, Y., & Tsukamoto, K. (2003) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.0000054199.78458.4b · Cited by 53
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Turning point: Mark Lawrence
Bell, A. (2012) · Nature · doi:10.1038/nj7398-407a · Cited by 52
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James, R., Searcy, J. L., Bihan, T. L., Martin, S. F., Gliddon, C. M., Povey, J. E., Deighton, R. F., Kerr, L. E., McCulloch, J., & Horsburgh, K. J. (2011) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2011.120 · Cited by 51
Apolipoprotein E decreases tau kinases and phospho-tau levels in primary neurons.
Hoe, H.-S., Freeman, J., & Rebeck, G. W. (2006) · Molecular Neurodegeneration · doi:10.1186/1750-1326-1-18 · Cited by 45
Effect of APOE genotype status on targeted clinical trials outcomes and efficiency in dementia and mild cognitive impairment resulting from Alzheimer's disease
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Impact of genetic factors on outcome from brain injury
Wilson, M. H., & Montgomery, H. (2007) · British Journal of Anaesthesia · doi:10.1093/bja/aem142 · Cited by 41
Human Apolipoprotein E4 Worsens Acute Axonal Pathology but Not Amyloid-β Immunoreactivity After Traumatic Brain Injury in 3×TG-AD Mice
Bennett, R. E., Esparza, T. J., Lewis, H. A., Kim, E., Mac Donald, C. L., Sullivan, P. M., & Brody, D. L. (2013) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e31828e24ab · Cited by 40
ApoE mimetic peptide decreases Aβ production in vitro and in vivo
Minami, S. S., Cordova, A., Cirrito, J. R., Tesoriero, J. A., Babus, L. W., Davis, G. C., Dakshanamurthy, S., Turner, R. S., Pak, D. T., Rebeck, G. W., et al. (2010) · Molecular Neurodegeneration · doi:10.1186/1750-1326-5-16 · Cited by 34
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Liu, Q. R., Wu, W., Fang, C.-L., Li, R., Liu, P., Lei, P., Hu, J., Sun, X., Zheng, Y.-Z., Zhao, Y., et al. (2011) · Molecular BioSystems · doi:10.1039/c1mb05019b · Cited by 29
Aβ20–29 peptide blocking apoE/Aβ interaction reduces full-length Aβ42/40 fibril formation and cytotoxicity in vitro
Hao, J., Zhang, W., Zhang, P., Liu, R., Liu, L., Lei, G., Su, C., Miao, J., & Li, Z. (2010) · Neuropeptides · doi:10.1016/j.npep.2010.03.001 · Cited by 26
Effect of apolipoprotein E and butyrylcholinesterase genotypes on cognitive response to cholinesterase inhibitor treatment at different stages of Alzheimer's disease
Patterson, C., Todd, S., & Passmore, A. P. (2010) · The Pharmacogenomics Journal · doi:10.1038/tpj.2010.61 · Cited by 24
Presymptomatic apolipoprotein E genotyping for Alzheimer's disease risk assessment and prevention
Schipper, H. M. (2011) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2010.06.003 · Cited by 16
Altering Mitochondrial Dysfunction as an Approach to Treating Alzheimer’s Disease
Colca, J. R., & Feinstein, D. L. (2012) · Advances in pharmacology · doi:10.1016/b978-0-12-394816-8.00005-2 · Cited by 14
Differential Effects of ApoE Isoforms on Dendritic Spines In Vivo: Linking an Alzheimer's Disease Risk Factor with Synaptic Alterations
Basak, J. M., & Kim, J. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.0505-10.2010 · Cited by 6 · cited 2×
“APOE isoforms may differentially affect synaptic plasticity and dendritic spine integrity via the modulation of spine elimination (Basak & Kim 2010); as a result of isoformdependent levels of APOE (Basak & Kim 2010, Dumanis et al. 2009); and by acting as signaling molecules through interactions…”
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Cacabelos R, 2012, Int. J. Alzheimer's Dis., 2012, 518901
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Sorted by citations

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Dubois, B., Hampel, H., Feldman, H. H., Scheltens, P., Aisen, P., Andrieu, S., Bakardjian, H., Benali, H., Bertram, L., Blennow, K., et al. (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.02.002 · Cited by 1,925
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Itzhaki, R. F., Lathe, R., Balin, B. J., Ball, M. J., Bearer, E. L., Braak, H., Bullido, M. J., Carter, C., Clerici, M., Cosby, S. L., et al. (2016) · Journal of Alzheimer’s Disease · doi:10.3233/jad-160152 · Cited by 532
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Self-citation
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Self-citation
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Self-citation
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Self-citation
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Self-citation
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Self-citation
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Self-citation
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Self-citation
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Authors: Yu, J.-T., Tan, L., & Hardy, J.
Affiliations: Qingdao University (CN)
UCL Queen Square Institute of Neurology (GB)
ORCID: Yu, Jin-Tai
Tan, Lan
Hardy, John
Venue: Annual Review of Neuroscience
Publisher: Annual Reviews
Published: 2014-07-08
Volume: 37
Issue: 1
Pages: 79-100
ISSN: 0147-006X (ISSN-L)
1545-4126
DOI: 10.1146/annurev-neuro-071013-014300
OpenAlex: W2097112082
Cited by: 394
References: 152
Citations by year: 2026: 7 · 2025: 15 · 2024: 27 · 2023: 20 · 2022: 26 · 2021: 32 · 2020: 39 · 2019: 46 · 2018: 47 · 2017: 46 · 2016: 46 · 2015: 27 · 2014: 14
FWCI: 5.19
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Annual Review of Neuroscience (publishedVersion)
PubMed (publishedVersion)
UCL Discovery (University College London) (submittedVersion)
Funders: National Natural Science Foundation of China (81000544, 81171209)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: apolipoprotein E, Alzheimer's disease, late-onset Alzheimer's disease, genetic risk factors, amyloid-beta, gene therapy, APOE genotyping, treatment options
MeSH terms: Alzheimer Disease, Apolipoproteins E, Brain, Genotype, Humans, Models, Biological, Signal Transduction, Amyloid beta-Peptides, tau Proteins, Genetic Predisposition to Disease, Molecular Targeted Therapy

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Apolipoprotein E in Alzheimer's Disease: An Update

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