The DOI matches its Crossref record; 51 of the 53 references it cites were found in a registry or an index.
Human APOE Isoform-Dependent Effects on Brain β-Amyloid Levels in PDAPP Transgenic Mice
Open accessAbstract
To investigate the role of human apolipoprotein E (apoE) on Abeta deposition in vivo, we crossed PDAPP mice lacking mouse Apoe to targeted replacement mice expressing human apoE (PDAPP/TRE2, PDAPP/TRE3, or PDAPP/TRE4). We then measured the levels of apoE protein and Abeta peptides in plasma, CSF, and brain homogenates in these mice at different ages. We also quantified the amount of brain Abeta and amyloid burden in 18-month-old mice. In young PDAPP/TRE4 mice that were analyzed at an age before brain Abeta deposition, we observed a significant decrease in the levels of apoE in CSF and brain when compared with age-matched mice expressing either human E2 or E3. The brain levels of Abeta42 in PDAPP/TRE4 mice were substantially elevated even at this very early time point. In older PDAPP/TRE4 mice, the levels of insoluble apoE protein increased in parallel to the dramatic rise in brain Abeta burden, and the majority of apoE was associated with Abeta. In TRE4 only mice, we also observed a significant decrease in the level of apoE in brain homogenates. Since the relative level of apoE mRNA was equivalent in PDAPP/TRE and TRE only mice, it appears that post-translational mechanisms influence the levels of apoE protein in brain (E4 < E3 << E2), resulting in early and dramatic apoE isoform-dependent effects on brain Abeta levels (E4 >> E3 > E2) that increase with age. Therapeutic strategies aimed at increasing the soluble levels of apoE protein, regardless of isoform, may effectively prevent and (or) treat Alzheimer's disease.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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?
In the citing paper
“Plaque deposition is increased with APOE4 compared with APOE2 and APOE3 in humans and transgenic mice expressing familial AD (FAD) mutations (FAD-Tg) (2)(3)(4)(5).”
From APOE4-specific Changes in Aβ Accumulation in a New Transgenic Mouse Model of Alzheimer Disease (2012) · cites this paper as [3]
In the citing paper
“For example, crossing apoE-targeted replacement mice (apoE-TR) (9) with PDAPP mice (10) delays plaque deposition from ϳ10 to 18 months, although once detected, plaque levels are greater with APOE4 than APOE3 (3).”
From APOE4-specific Changes in Aβ Accumulation in a New Transgenic Mouse Model of Alzheimer Disease (2012) · cites this paper as [3]
In the citing paper
“Introduction of human APOE to existing FAD-Tg mice significantly delays plaque deposition, although once detected, plaque levels are generally greater with APOE4 than APOE3 (3, 6 -8).”
From APOE4-specific Changes in Aβ Accumulation in a New Transgenic Mouse Model of Alzheimer Disease (2012) · cites this paper as [3]
In the citing paper
“Crossing a transgenic mouse model of AD that has high levels of human Aβ in the brain with human APOE targeted replacement mice demonstrated age-dependent and APOE isoform-dependent (E4>>E3>E2) Aβ deposition and amyloid burden in the brain in a manner that recapitulates the human condition observed in pre-symptomatic elderly APOE4 carriers as well as AD patients.18–21”
From AAVrh.10-Mediated APOE2 Central Nervous System Gene Therapy for APOE4-Associated Alzheimer's Disease (2018) · cites this paper as [18]
In the citing paper
“Even in homozygous APOE2/2 mice, prior reports have been inconsistent regarding further reductions in amyloid pathology compared with APOE3/3 , re fl ecting ongoing debate 34,48,49 .”
From APOE2 attenuates APOE4-associated amyloid pathology and related toxicity in a mouse model of Alzheimer’s disease (2026) · cites this paper as [49]
In the citing paper
“we and others have reported human apoE isoform-dependent differences in amyloid plaque deposition in APP-transgenic mice (E4 > E3 > E2) (10-14).”
From Human ApoE isoforms differentially regulate brain amyloid-β peptide clearance (2011) · cites this paper as [14]
In the citing paper
“Although there are some conflicting studies (61), several groups have reported that the concentration of apoE in the brains of human apoE knock-in mice varies in an apoE isoform-dependent manner, that is, E2>E3>E4 (14, 62, 63).”
From Human ApoE isoforms differentially regulate brain amyloid-β peptide clearance (2011) · cites this paper as [14]
In the citing paper
“though apoE concentration differences are unlikely to completely account for Aβ metabolism differences in the setting of apoE3 versus apoE4 (14)”
From Human ApoE isoforms differentially regulate brain amyloid-β peptide clearance (2011) · cites this paper as [14]
In the citing paper
“APOE isoform-dependent amyloid deposition has been consistently observed in humans and Aβ depositing mouse models (Holtzman et al., 2000; Bales et al., 2009; Reiman et al., 2009; Morris et al., 2010).”
From Haploinsufficiency of Human APOE Reduces Amyloid Deposition in a Mouse Model of Amyloid-β Amyloidosis (2011) · cites this paper as Bales et al., 2009
In the citing paper
“In fact, we have previously demonstrated that APP/ε4 and PDAPP/ε4 mice have greatly increased content of apoE within Aβ deposits compared to the same Tg mice lines expressing other human APOE alleles [19, 36].”
From APOE Genotype Differentially Modulates Effects of Anti-Aβ, Passive Immunization in APP Transgenic Mice (2017) · cites this paper as [36]
In the citing paper
“VAβ is detrimental to the function of cerebrovascular circulation through compromising blood–brain-barrier integrity [49], effecting hemodynamic dysfunction [29, 50], and facilitating occurrence of spontaneous hemorrhages [25, 26, 36].”
From APOE Genotype Differentially Modulates Effects of Anti-Aβ, Passive Immunization in APP Transgenic Mice (2017) · cites this paper as [36]
In the citing paper
“Thus far, the differential effect of targeted ApoE isoform replacement on Ab pathology has been reproduced in single APP V717F mice, which had to be at least 18 months of age to observe substantial Ab load.56,57”
From Blocking the Interaction between Apolipoprotein E and Aβ Reduces Intraneuronal Accumulation of Aβ and Inhibits Synaptic Degeneration (2013) · cites this paper as [56]
In the citing paper
“there are apoE isoform-dependent effects (E4>E3>E2) on promoting brain Aβ deposition in PDAPP transgenic mice”
From ApoE4 reduction: An emerging and promising therapeutic strategy for Alzheimer's disease (2022) · cites this paper as Bales et al 2009
In the citing paper
“APOE4-targeted replacement mice, expressing the human APOE4 allele instead of the mouse Apoe, crossed with different AD mouse models such as PDAPP, APP/ PS1ΔE9 and 5xFAD, accelerated plaque formation compared to APOE3-targeted replacement mice (Bales et al, 2009; Castellano et al, 2011; Fagan et al, 2002; Holtzman et al, 2000a; Rodriguez et al, 2014; Youmans et al, 2012).”
From APOE from astrocytes restores Alzheimer’s Aβ-pathology and DAM-like responses in APOE deficient microglia (2024) · cites this paper as Bales et al, 2009
In the citing paper
“Nevertheless other studies have also reported that APOE2 expression is associated with similar or even higher plaque load than APOE3 (Rodriguez et al, 2014; Youmans et al, 2012; Bales et al, 2009; Dodart et al, 2005).”
From APOE from astrocytes restores Alzheimer’s Aβ-pathology and DAM-like responses in APOE deficient microglia (2024) · cites this paper as Bales et al, 2009
In the citing paper
“It has also been shown that APOE2 expression leads to increased APOE levels in mouse models and human brain (Riddell et al, 2008; Bales et al, 2009; Conejero-Goldberg et al, 2014), which can influence amyloid pathology.”
From APOE from astrocytes restores Alzheimer’s Aβ-pathology and DAM-like responses in APOE deficient microglia (2024) · cites this paper as Bales et al, 2009
In the citing paper
“Recently, PDAPP mice bred to apoE2, E3, and apoE4 knock-in mice demonstrated a clear isoform-dependent (E4>E3>E2) effect on Aβ accumulation (Bales et al., 2009).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Bales et al., 2009
In the citing paper
“In agreement with our data, significantly reduced ApoE levels were also observed in hiPSC-derived ApoE4 astrocytes [15,16,24], as well as in brain homogenates from mouse models expressing the human ApoE4 isoform [43,44].”
From ApoE3 vs. ApoE4 Astrocytes: A Detailed Analysis Provides New Insights into Differences in Cholesterol Homeostasis (2022) · cites this paper as [44]
In the citing paper
“This is further complicated by the fact that expression of different isoforms of human ApoE in transgenic mice results in different levels of plaque and CAA burden with apoE4 expression enhancing amyloid deposition compared to apoE3 or apoE2 [3, 21, 40, 59, 86, 178].”
From Alzheimer's disease: experimental models and reality (2017) · cites this paper as [3]
Citations
Cites
Association of apolipoprotein E allele ϵ4 with late‐onset familial and sporadic Alzheimer's disease
Saunders, A. M., Strittmatter, W. J., Schmechel, D., St. George-Hyslop, P. H., Pericak-Vance, M. A., Joo, S. H., Rosi, B. L., Gusella, J. F., Crapper-MacLachlan, D. R., Alberts, M. J., et al. (1993) · Neurology · doi:10.1212/wnl.43.8.1467 · Cited by 3,786
Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease
Corder, E. H., Saunders, A. M., Risch, N. J., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Rimmler, J. B., Locke, P. A., Conneally, P. M., Schmader, K. E., et al. (1994) · Nature Genetics · doi:10.1038/ng0694-180 · Cited by 1,920
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
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
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
Self-citationMahley, R. W., Weisgraber, K. H., & Huang, Y. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0600549103 · Cited by 912
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
Apolipoprotein E: Structure-Function Relationships
Weisgraber, K. H. (1994) · Advances in Protein Chemistry · doi:10.1016/s0065-3233(08)60642-7 · Cited by 830
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
Self-citationBoyles, J. K., Pitas, R. E., Wilson, E., Mahley, R. W., & Taylor, J. M. (1985) · Journal of Clinical Investigation · doi:10.1172/jci112130 · Cited by 829
Research works printed but not linked: 1
- 10.1001/jama.1997.03540340052032 · DOI
Cited by
Sorted by citations
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
Alzheimer Disease: An Update on Pathobiology and Treatment Strategies
Long, J. M., & Holtzman, D. M. (2019) · Cell · doi:10.1016/j.cell.2019.09.001 · Cited by 3,204
Alzheimer Mechanisms and Therapeutic Strategies
Huang, Y., & Mucke, L. (2012) · Cell · doi:10.1016/j.cell.2012.02.040 · Cited by 1,758
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
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
“Interaction of nascent ApoE2, ApoE3, and ApoE4 isoforms expressed in mammalian cells with amyloid peptide beta (1-40).”
InfluentialSelf-citationApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy
Initiative, A. D. N., Shi, Y., Yamada, K., Liddelow, S. A., Smith, S. T., Zhao, L., Luo, W., Tsai, R. M., Spina, S., Grinberg, L. T., et al. (2017) · Nature · doi:10.1038/nature24016 · Cited by 1,220
Self-citationThe Amyloid Beta Peptide: A Chemist’s Perspective. Role in Alzheimer’s and Fibrillization
Hamley, I. W. (2012) · Chemical Reviews · doi:10.1021/cr3000994 · Cited by 892
Apolipoprotein E in Alzheimer’s disease and other neurological disorders
Verghese, P. B., Castellano, J. M., & Holtzman, D. M. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70325-2 · Cited by 857
Alzheimer's disease: experimental models and reality
Drummond, E., & Wisniewski, T. (2017) · Acta Neuropathologica · doi:10.1007/s00401-016-1662-x · Cited by 810
ApoE in Alzheimer’s disease: pathophysiology and therapeutic strategies
Raulin, A.-C., Doss, S. V., Trottier, Z. A., Ikezu, T. C., Bu, G., & Liu, C.-C. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00574-4 · Cited by 756
The role of microglia in amyloid clearance from the AD brain
Lee, C. Y. D., & Landreth, G. E. (2010) · Journal of Neural Transmission · doi:10.1007/s00702-010-0433-4 · Cited by 701
ApoE and Aβ in Alzheimer’s Disease: Accidental Encounters or Partners?
Kanekiyo, T., Xu, H., & Bu, G. (2014) · Neuron · doi:10.1016/j.neuron.2014.01.045 · Cited by 608
Biochemistry of Amyloid -Protein and Amyloid Deposits in Alzheimer DiseasePreprint
Masters, C. L., & Selkoe, D. J. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006262 · Cited by 554
ApoE4 Accelerates Early Seeding of Amyloid Pathology
Liu, C.-C., Zhao, N., Fu, Y., Wang, N., Linares, C., Tsai, C.-W., & Bu, G. (2017) · Neuron · doi:10.1016/j.neuron.2017.11.013 · Cited by 451
Amyloid toxicity in Alzheimer’s disease
Reiss, A. B., Arain, H. A., Stecker, M. M., Siegart, N. M., & Kasselman, L. J. (2018) · Reviews in the Neurosciences · doi:10.1515/revneuro-2017-0063 · Cited by 447
Apolipoprotein E in Alzheimer's Disease: An Update
Yu, J.-T., Tan, L., & Hardy, J. (2014) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-071013-014300 · Cited by 394
Apolipoprotein E, Receptors, and Modulation of Alzheimer’s Disease
Zhao, N., Liu, C.-C., Qiao, W., & Bu, G. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.03.003 · Cited by 370
New Insights Into the Pathogenesis of Alzheimer's Disease
Fan, L., Mao, C., Hu, X., Zhang, S., Yang, Z., Hu, Z., Sun, H., Fan, Y., Dong, Y., Yang, J., et al. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2019.01312 · Cited by 362
Dysregulation of cholesterol balance in the brain: contribution to neurodegenerative diseases
Vance, J. E. (2012) · Disease Models & Mechanisms · doi:10.1242/dmm.010124 · Cited by 342
Mouse models of Alzheimer's disease
Hall, A. M., & Roberson, E. D. (2012) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2011.11.017 · Cited by 317
Genes associated with Alzheimer's disease: an overview and current status
Giri, M., Lü, Y., & Zhang, M. (2016) · Clinical Interventions in Aging · doi:10.2147/cia.s105769 · Cited by 311
APOE2: protective mechanism and therapeutic implications for Alzheimer’s disease
Li, Z., Shue, F., Zhao, N., Shinohara, M., & Bu, G. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00413-4 · Cited by 306
Apolipoprotein E: Structural Insights and Links to Alzheimer Disease Pathogenesis
Chen, Y., Strickland, M. R., Soranno, A., & Holtzman, D. M. (2021) · Neuron · doi:10.1016/j.neuron.2020.10.008 · Cited by 298
Shinohara, M., Tachibana, M., Kanekiyo, T., & Bu, G. (2017) · Journal of Lipid Research · doi:10.1194/jlr.r075796 · Cited by 297
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
Nishitsuji, K., Hosono, T., Nakamura, T., Bu, G., & Michikawa, M. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.225532 · Cited by 275
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
“Importantly, APOE4 is associated with a higher plaque burden than APOE2 and APOE3 (53).”
BackgroundResultInfluentialAPOE mediated neuroinflammation and neurodegeneration in Alzheimer’s disease
Parhizkar, S., & Holtzman, D. M. (2022) · Seminars in Immunology · doi:10.1016/j.smim.2022.101594 · Cited by 255
Ungar, L., Altmann, A., & Greicius, M. D. (2014) · Brain Imaging and Behavior · doi:10.1007/s11682-013-9272-x · Cited by 246
Are NSAIDs useful to treat Alzheimer’s disease or mild cognitive impairment
Imbimbo (2010) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2010.00019 · Cited by 75
Evidence for impaired amyloid β clearance in Alzheimer's disease
Wildsmith, K. R., Holley, M., Savage, J. C., Skerrett, R., & Landreth, G. E. (2013) · Alzheimer s Research & Therapy · doi:10.1186/alzrt187 · Cited by 249
Uddin, M. S., Kabir, M. T., Al Mamun, A., Abdel-Daim, M. M., Barreto, G. E., & Ashraf, G. M. (2019) · Molecular Neurobiology · doi:10.1007/s12035-018-1237-z · Cited by 212
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
The duality of amyloid-β: its role in normal and Alzheimer’s disease states
Azargoonjahromi, A. (2024) · Molecular Brain · doi:10.1186/s13041-024-01118-1 · Cited by 214
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
APOE2 enhances neuroprotection against Alzheimer’s disease through multiple molecular mechanisms
Conejero-Goldberg, C., Gomar, J. J., Bobes-Bascaran, T., Hyde, T. M., Kleinman, J. E., Herman, M. M., Chen, S., Davies, P., & Goldberg, T. E. (2014) · Molecular Psychiatry · doi:10.1038/mp.2013.194 · Cited by 199
Human APOE4 increases microglia reactivity at Aβ plaques in a mouse model of Aβ deposition
Rodriguez, G. A., Tai, L. M., LaDu, M. J., & Rebeck, G. W. (2014) · Journal of Neuroinflammation · doi:10.1186/1742-2094-11-111 · Cited by 193
The Role of APOE and TREM2 in Alzheimer′s Disease—Current Understanding and Perspectives
Wolfe, C. M., Fitz, N. F., Nam, K. N., Lefterov, I. M., & Koldamova, R. P. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms20010081 · Cited by 201
On phagocytes and macular degeneration
Guillonneau, X., Eandi, C. M., Paques, M., Sahel, J.-A., Sapieha, P., & Sennlaub, F. (2017) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2017.06.002 · Cited by 185
Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer’s disease
Najm, R., Jones, E. A., & Huang, Y. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0324-6 · Cited by 183
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
Pathways to Alzheimer's disease
Hardy, J., Bogdanović, N., Winblad, B. G., Portelius, E., Andreasen, N. C., Cedazo-Mínguez, Á., & Zetterberg, H. (2014) · Journal of Internal Medicine · doi:10.1111/joim.12192 · Cited by 180
APOE genotype regulates pathology and disease progression in synucleinopathy
Davis, A. A., Inman, C. E., Wargel, Z. M., Dube, U., Freeberg, B. M., Galluppi, A., Haines, J. N., Dhavale, D. D., Miller, R., Choudhury, F. A., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aay3069 · Cited by 177
Self-citationBien-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
AAVrh.10-Mediated APOE2 Central Nervous System Gene Therapy for APOE4-Associated Alzheimer's Disease
Rosenberg, J. B., Kaplitt, M. G., De, B. P., Chen, A., Flagiello, T., Salami, C., Pey, E., Zhao, L., Ricart Arbona, R. J., Monette, S., et al. (2018) · Human Gene Therapy Clinical Development · doi:10.1089/humc.2017.231 · Cited by 176
Self-citationYamazaki, Y., Painter, M. M., Bu, G., & Kanekiyo, T. (2016) · CNS Drugs · doi:10.1007/s40263-016-0361-4 · Cited by 173
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
Hu, J., Liu, C.-C., Chen, X.-F., Zhang, Y.-W., Xu, H., & Bu, G. (2015) · Molecular Neurodegeneration · doi:10.1186/s13024-015-0001-3 · Cited by 161
Duan, L., Bhattacharyya, B. J., Belmadani, A. A., Pan, L., Miller, R. J., & Kessler, J. A. (2014) · Molecular Neurodegeneration · doi:10.1186/1750-1326-9-3 · Cited by 165
APOE and cholesterol homeostasis in Alzheimer's disease
Leduc, V., Jasmin, S. B., & Poirier, J. (2010) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2010.07.008 · Cited by 166
Castellano, J. M., Deane, R., Gottesdiener, A. J., Verghese, P. B., Stewart, F. R., West, T., Paoletti, A. C., Kasper, T. R., DeMattos, R. B., Zlokovic, B. V., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1206446109 · Cited by 154
APOE-ε2 and APOE-ε4 Correlate With Increased Amyloid Accumulation in Cerebral Vasculature
Nelson, P. T., Pious, N. M., Jicha, G. A., Wilcock, D. M., Fardo, D. W., Estus, S., & Rebeck, G. W. (2013) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e31829a25b9 · Cited by 150
Huynh, T.-P. V., Wang, C., Tran, A. C., Tabor, G. T., Mahan, T. E., Francis, C. M., Finn, M. B., Spellman, R., Manis, M., Tanzi, R. E., et al. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0337-1 · Cited by 139
Fitz, N. F., Cronican, A. A., Saleem, M., Fauq, A. H., Chapman, R., Lefterov, I., & Koldamova, R. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.1937-12.2012 · Cited by 119
Molecular mechanisms linking amyloid β toxicity and Tau hyperphosphorylation in Alzheimer׳s disease
Lloret, A., Fuchsberger, T., Giraldo, E., & Viña, J. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.02.028 · Cited by 135
In vivo measurement of apolipoprotein E from the brain interstitial fluid using microdialysis
Ulrich, J. D., Burchett, J. M., Restivo, J. L., Schuler, D. R., Verghese, P. B., Mahan, T. E., Landreth, G. E., Castellano, J. M., Jiang, H., Cirrito, J. R., et al. (2013) · Molecular Neurodegeneration · doi:10.1186/1750-1326-8-13 · Cited by 128
Rasmussen, K. L. (2016) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2016.10.037 · Cited by 125
APOE-amyloid interaction: Therapeutic targets
Wisniewski, T., & Drummond, E. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104784 · Cited by 131
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
Alzheimer's Disease and the Amyloid β-Protein
Walsh, D. M., & Teplow, D. B. (2012) · Progress in molecular biology and translational science · doi:10.1016/b978-0-12-385883-2.00012-6 · Cited by 121
Soluble apoE/Aβ complex: mechanism and therapeutic target for APOE4-induced AD risk
Tai, L. M., Mehra, S., Shete, V., Estus, S., Rebeck, G. W., Bu, G., & LaDu, M. J. (2014) · Molecular Neurodegeneration · doi:10.1186/1750-1326-9-2 · Cited by 116
ACAT1/SOAT1 as a Therapeutic Target for Alzheimer's Disease
Shibuya, Y., Chang, C. C., & Chang, T.-Y. (2015) · Future Medicinal Chemistry · doi:10.4155/fmc.15.161 · Cited by 113
APOE2 eases cognitive decline during Aging: Clinical and preclinical evaluations
Shinohara, M., Kanekiyo, T., Yang, L., Linthicum, D., Shinohara, M., Fu, Y., Price, L., Frisch‐Daiello, J. L., Han, X., Fryer, J. D., et al. (2016) · Annals of Neurology · doi:10.1002/ana.24628 · Cited by 111
Ai, J., Sun, L., Che, H., Zhang, R., Zhang, T.-Z., Wu, W.-C., Su, X., Chen, X., Yang, G., Li, K., et al. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.1997-12.2013 · Cited by 109
Zhao, L., Gottesdiener, A. J., Parmar, M., Li, M., Kaminsky, S. M., Chiuchiolo, M. J., Sondhi, D., Sullivan, P. M., Holtzman, D. M., Crystal, R. G., et al. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.04.020 · Cited by 107
Self-citationKeene, 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
Impact of Apolipoprotein E on Alzheimer’s Disease
Hauser, P. S., & Ryan, R. O. (2013) · Current Alzheimer Research · doi:10.2174/15672050113109990156 · Cited by 103
Iliyasu, M. O., Musa, S. A., Oladele, S. B., & Iliya, A. I. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1081938 · Cited by 106
Animal models of dementia and cognitive dysfunction
Neha, N., Sodhi, R. K., Jaggi, A. S., & Singh, N. (2014) · Life Sciences · doi:10.1016/j.lfs.2014.05.017 · Cited by 104
Apolipoprotein E, amyloid-beta, and neuroinflammation in Alzheimer’s disease
Dorey, E., Chang, N., Liu, Q. Y., Yang, Z., & Zhang, W. (2014) · Neuroscience Bulletin · doi:10.1007/s12264-013-1422-z · Cited by 105
APOE Isoforms Control Pathogenic Subretinal Inflammation in Age-Related Macular Degeneration
Levy, O., Lavalette, S., Hu, S. J., Housset, M., Raoul, W., Eandi, C. M., Sahel, J., Sullivan, P. M., Guillonneau, X., & Sennlaub, F. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.2468-15.2015 · Cited by 101
Self-citationApolipoprotein E and lipid homeostasis in the etiology and treatment of sporadic Alzheimer's disease
Poirier, J., Miron, J., Picard, C., Gormley, P., Théroux, L., Breitner, J. C. S., & Dea, D. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.03.037 · Cited by 101
Moving beyond amyloid and tau to capture the biological heterogeneity of Alzheimer’s disease
Young‐Pearse, T. L., Lee, H., Hsieh, Y., Chou, V., & Selkoe, D. J. (2023) · Trends in Neurosciences · doi:10.1016/j.tins.2023.03.005 · Cited by 104
Simon, R., Girod, M., Fonbonne, C., Salvador, A., Clément, Y., Lantéri, P., Amouyel, P., Lambert, J. C., & Lemoine, J. (2012) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m112.018861 · Cited by 92
Jendresen, C., Årskog, V., Daws, M. R., & Nilsson, L. N. G. (2017) · Journal of Neuroinflammation · doi:10.1186/s12974-017-0835-4 · Cited by 94
Cerf, E., Gustot, A., Goormaghtigh, E., Ruysschaert, J.-M., & Raussens, V. (2011) · The FASEB Journal · doi:10.1096/fj.10-175976 · Cited by 92
EFAD transgenic mice as a human APOE relevant preclinical model of Alzheimerʼns disease
Tai, L. M., Balu, D., Avila-Munoz, E., Abdullah, L., Thomas, R., Collins, N., Valencia-Olvera, A. C., & LaDu, M. J. (2017) · Journal of Lipid Research · doi:10.1194/jlr.r076315 · Cited by 93
Amyloid-β Pathology and APOE Genotype Modulate Retinoid X Receptor Agonist Activity in Vivo
Tai, L. M., Koster, K. P., Luo, J., Lee, S. H., Wang, Y.-T., Collins, N. C., Ben Aissa, M., Thatcher, G. R. J., & LaDu, M. J. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.600833 · Cited by 89
Retinoids as potential targets for Alzheimer's disease
Sodhi, R. K., & Singh, N. (2014) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2014.02.016 · Cited by 94
Absolute 10-year risk of dementia by age, sex and APOE genotype: a population-based cohort study
Rasmussen, K. L., Tybjærg-Hansen, A., Nordestgaard, B. G., & Frikke-Schmidt, R. (2018) · Canadian Medical Association Journal · doi:10.1503/cmaj.180066 · Cited by 91
ECM receptors in neuronal structure, synaptic plasticity, and behavior
Kerrisk, M. E., Cingolani, L. A., & Koleske, A. J. (2014) · Progress in brain research · doi:10.1016/b978-0-444-63486-3.00005-0 · Cited by 96
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
“Thus far, the differential effect of targeted ApoE isoform replacement on Ab pathology has been reproduced in single APPV717F mice, which had to be at least 18 months of age to observe substantial Ab load.(56,57) Thus, APPSW/PS1dE9/ApoE-TR mice represent an important advance in modeling the effect of human ApoE isofor…”
BackgroundSelf-citationLaws, S. M., Gaskin, S., Woodfield, A., Srikanth, V. K., Bruce, D. G., Fraser, P. E., Porter, T., Newsholme, P., Wijesekara, N., Burnham, S. C., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-09577-4 · Cited by 98
Skerrett, R., Pellegrino, M. P., Casali, B. T., Taraboanta, L., & Landreth, G. E. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.652008 · Cited by 91
Quercetin stabilizes apolipoprotein E and reduces brain Aβ levels in amyloid model mice
Zhang, X., Hu, J., Zhong, L., Wang, N., Yang, L., Liu, C., Li, H., Wang, X., Zhou, Y., Zhang, Y., et al. (2016) · Neuropharmacology · doi:10.1016/j.neuropharm.2016.04.032 · Cited by 85
The Oxygen Paradox, the French Paradox, and age-related diseases
Davies, J. M. S., Cillard, J., Friguet, B., Cadenas, E., Cadet, J., Cayce, R., Fishmann, A., Liao, D., Bulteau, A.-L., Derbré, F., et al. (2017) · GeroScience · doi:10.1007/s11357-017-0002-y · Cited by 82
Association of APOE e2 genotype with Alzheimer’s and non-Alzheimer’s neurodegenerative pathologies
Goldberg, T. E., Huey, E. D., & Devanand, D. P. (2020) · Nature Communications · doi:10.1038/s41467-020-18198-x · Cited by 82
The role of APOE in transgenic mouse models of AD
Balu, D., Karstens, A. J., Loukenas, E., Maldonado Weng, J., York, J. M., Valencia-Olvera, A. C., & LaDu, M. J. (2019) · Neuroscience Letters · doi:10.1016/j.neulet.2019.134285 · Cited by 81
Murine models of Alzheimer's disease and their use in developing immunotherapies
Wısnıewskı, T., & Sigurdsson, E. M. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2010.05.004 · Cited by 84
Liao, F., Zhang, T. J., Jiang, H., Lefton, K. B., Robinson, G. O., Vassar, R., Sullivan, P. M., & Holtzman, D. M. (2015) · Acta Neuropathologica Communications · doi:10.1186/s40478-015-0250-y · Cited by 77
Self-citationCholesterol-related genes in Alzheimer's disease
Wollmer, M. A. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2010.05.009 · Cited by 78
Amyloid-β42 alters apolipoprotein E solubility in brains of mice with five familial AD mutations
Youmans, K. L., Leung, S., Zhang, J., Maus, E., Baysac, K., Bu, G., Vassar, R., Yu, C., & LaDu, M. J. (2011) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2010.12.025 · Cited by 62
Fruhwürth, S., Zetterberg, H., & Paludan, S. R. (2024) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2024.578342 · Cited by 77
The beneficial effects of HMG-CoA reductase inhibitors in the processes of neurodegeneration
Saravi, S. S. S., Saravi, S. S. S., Arefidoust, A., & Dehpour, A. R. (2017) · Metabolic Brain Disease · doi:10.1007/s11011-017-0021-5 · Cited by 77
Understanding the cause of sporadic Alzheimer’s disease
Zetterberg, H., & Mattsson, N. (2014) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.2014.915740 · Cited by 73
APOE4 confers transcriptomic and functional alterations to primary mouse microglia
Machlovi, S. I., Neuner, S. M., Hemmer, B. M., Khan, R., Liu, Y., Huang, M., Zhu, J. D., Castellano, J. M., Cai, D., Marcora, E., et al. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105615 · Cited by 73
Insulin: An Emerging Treatment for Alzheimer’s Disease Dementia?
Morris, J. K., & Burns, J. M. (2012) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-012-0297-0 · Cited by 72
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
Shinohara, M., Petersen, R. C., Dickson, D. W., & Bu, G. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1086-9 · Cited by 56
Lewandowski, C. T., Maldonado Weng, J., & LaDu, M. J. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104811 · Cited by 72
Metadata
- Authors
- Bales, K. R., Liu, F., Wu, S., Lin, S., Koger, D., DeLong, C., Hansen, J. C., Sullivan, P. M., & Paul, S. M.
- Affiliations
- Eli Lilly (United States) (US)
- Duke University (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2009-05-27
- Volume
- 29
- Issue
- 21
- Pages
- 6771-6779
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6665579
- OpenAlex
- W2066673859
- Cited by
- 274
- References
- 53
- Citations by year
- 2026: 2 · 2025: 13 · 2024: 16 · 2023: 14 · 2022: 18 · 2021: 12 · 2020: 20 · 2019: 12 · 2018: 13 · 2017: 22 · 2016: 15 · 2015: 12 · 2014: 22 · 2013: 18 · 2012: 24
- FWCI
- 14.36
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- 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, APOE isoforms, amyloid-beta deposition, amyloid burden, cerebrospinal fluid, brain amyloid, amyloid-beta 42, post-translational regulation, Alzheimer's disease
- MeSH terms
- Age Factors, Analysis of Variance, Animals, Apolipoproteins E, Brain, Humans, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Peptide Fragments, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Protein Isoforms, Mice
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
