Apolipoprotein E fragments present in Alzheimer's disease brains induce neurofibrillary tangle-like intracellular inclusions in neurons
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Human apolipoprotein (apo) E4, a major risk factor for Alzheimer's disease (AD), occurs in amyloid plaques and neurofibrillary tangles (NFTs) in AD brains; however, its role in the pathogenesis of these lesions is unclear. Here we demonstrate that carboxyl-terminal-truncated forms of apoE, which occur in AD brains and cultured neurons, induce intracellular NFT-like inclusions in neurons. These cytosolic inclusions were composed of phosphorylated tau, phosphorylated neurofilaments of high molecular weight, and truncated apoE. Truncated apoE4, especially apoE4(Δ272–299), induced inclusions in up to 75% of transfected neuronal cells, but not in transfected nonneuronal cells. ApoE4 was more susceptible to truncation than apoE3 and resulted in much greater intracellular inclusion formation. These results suggest that apoE4 preferentially undergoes intracellular processing, creating a bioactive fragment that interacts with cytoskeletal components and induces NFT-like inclusions containing phosphorylated tau and phosphorylated neurofilaments of high molecular weight in neurons.
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The truncated apoE4 variant apoE4[Δ(166-299)] has a similar molecular weight to carboxyl-terminal truncated apoE4 fragments found in the brain of Alzheimer disease patients.
“which has a similar molecular weight as carboxyl-terminal truncated apoE4 fragments found in the brain of AD patients (54,55)”
From Molecular Basis for Increased Risk for Late-onset Alzheimer Disease Due to the Naturally Occurring L28P Mutation in Apolipoprotein E4 (2014) · cites this paper as [54]
Prior association studies of L28P with late-onset Alzheimer's disease used relatively limited samples.
“The original association study implicating L28P with LOAD risk was carried out in a relatively small sample size.”
From Investigation of the independent role of a rare APOE variant (L28P; APOE*4Pittsburgh) in late-onset Alzheimer disease (2023) · cites this paper as [13]
L28P has been examined in additional Alzheimer's disease case-control samples since its initial identification.
“Since then, this variant has been examined in additional AD case-control samples [11–13]”
From Investigation of the independent role of a rare APOE variant (L28P; APOE*4Pittsburgh) in late-onset Alzheimer disease (2023) · cites this paper as [13]
APOE4 expression generates a toxic C-terminal fragment of apoE4 that can directly target electron transport chain (ETC) complexes in mitochondria.
“the generation of a toxic C-terminal fragment of apoE4 that can directly target electron transport chain (ETC) complexes in the mitochondria25–27”
From APOE4 is Associated with Differential Regional Vulnerability to Bioenergetic Deficits in Aged APOE Mice (2020) · cites this paper as [26]
The single amino acid difference increases apoE4 cleavage by a stress-induced neuron-specific protease.
“increases its cleavage by a stress-induced neuron-specific protease [7, 12, 16]”
From Neuronal Apolipoprotein E4 Expression Results in Proteome-Wide Alterations and Compromises Bioenergetic Capacity by Disrupting Mitochondrial Function (2019) · cites this paper as [16]
ApoE4 potentiates the aggregation of P-tau into NFT-like inclusions in transfected primary neurons.
“this ApoE isoform potentiates the aggregation of P-tau into NFT-like inclusions in transfected primary neurons [51]”
From Apoe4 and Alzheimer’s Disease Pathogenesis—Mitochondrial Deregulation and Targeted Therapeutic Strategies (2023) · cites this paper as [51]
ApoE4 interacts directly with NFTs in AD brains.
“ApoE4 has been demonstrated to interact directly with NFTs in AD brains”
From Apoe4 and Alzheimer’s Disease Pathogenesis—Mitochondrial Deregulation and Targeted Therapeutic Strategies (2023) · cites this paper as [51]
ApoE4 is highly susceptible to neuron-specific proteolysis, which generates neurotoxic fragments.
“As mentioned above, apoE4 is highly susceptible to neuron-specific proteolysis, which generates neurotoxic fragments [20, 77–79].”
From Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer’s disease (2019) · cites this paper as [78]
ApoE4 is associated with higher microglial cell reactivity around amyloid-β plaques than ApoE3 in deep cortical layers.
“Of note, ApoE4 is associated with higher microglial cell reactivity around amyloid-β plaques than ApoE3 in deep cortical layers125.”
From Interplay between innate immunity and Alzheimer disease: APOE and TREM2 in the spotlight (2018) · cites this paper as [125]
Cites
The Metabolic and Molecular Bases of Inherited Disease
Scriver, R. C. (1995) · Medical Entomology and Zoology · Cited by 12,101 · see citing works
Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., Roses, A. D., Haines, J. L., & Pericak-Vance, M. A. (1993) · Science · doi:10.1126/science.8346443 · Cited by 9,429 · see citing works
The metabolic and molecular bases of inherited disease
Chen, Y.-T. (2001) · Medical Entomology and Zoology · Cited by 6,928 · see citing works
Strittmatter, W. J., Saunders, A. M., Schmechel, D., Pericak-Vance, M., Enghild, J., Salvesen, G. S., & Roses, A. D. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.5.1977 · Cited by 4,268 · see citing works
Apolipoprotein E: Cholesterol Transport Protein with Expanding Role in Cell Biology
Mahley, R. W. (1988) · Science · doi:10.1126/science.3283935 · Cited by 4,028 · see citing works
Self-citationThe molecular pathology of Alzheimer's disease
Selkoe, D. J. (1991) · Neuron · doi:10.1016/0896-6273(91)90052-2 · Cited by 2,708 · 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
Self-citationLewis, J., McGowan, E., Rockwood, J., Melrose, H., Nacharaju, P., Van Slegtenhorst, M., Gwinn-Hardy, K., Murphy, M. P., Baker, M., Yu, X., et al. (2000) · Nature Genetics · doi:10.1038/78078 · Cited by 1,371 · see citing works
Strittmatter, W. J., Weisgraber, K. H., Huang, D. Y., Dong, L. M., Salvesen, G. S., Pericak-Vance, M., Schmechel, D., Saunders, A. M., Goldgaber, D., & Roses, A. D. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.17.8098 · Cited by 1,363 · see citing works
Namba, Y., Tomonaga, M., Kawasaki, H., Otomo, E., & Ikeda, K. (1991) · Brain Research · doi:10.1016/0006-8993(91)91092-f · Cited by 1,157 · see citing works
Ma, J., Yee, A., Brewer, H. B., Das, S., & Potter, H. (1994) · Nature · doi:10.1038/372092a0 · Cited by 871 · see citing works
Apolipoprotein E: a pathological chaperone protein in patients with cerebral and systemic amyloid
Wisniewski, T., & Frangione, B. (1992) · Neuroscience Letters · doi:10.1016/0304-3940(92)90444-c · Cited by 802 · see citing works
Differential Effects of Apolipoproteins E3 and E4 on Neuronal Growth in Vitro
Nathan, B. P., Bellosta, S., Sanan, D. A., Weisgraber, K. H., Mahley, R. W., & Pitas, R. E. (1994) · Science · doi:10.1126/science.8171342 · Cited by 795 · see citing works
Self-citationPleasure, S., Page, C., & Lee, V. (1992) · Journal of Neuroscience · doi:10.1523/jneurosci.12-05-01802.1992 · Cited by 607 · see citing works
Ishihara, T., Hong, M., Zhang, B., Nakagawa, Y., Lee, M. K., Trojanowski, J. Q., & Lee, V. M.-Y. (1999) · Neuron · doi:10.1016/s0896-6273(00)81127-7 · Cited by 564 · see citing works
Isoform-specific binding of apolipoprotein E to beta-amyloid.
LaDu, M. J., Falduto, M. T., Manelli, A. M., Reardon, C. A., Getz, G. S., & Frail, D. E. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)31529-6 · Cited by 540 · see citing works
Strittmatter, W. J., Saunders, A. M., Goedert, M., Weisgraber, K. H., Dong, L. M., Jakes, R., Huang, D. Y., Pericak-Vance, M., Schmechel, D., & Roses, A. D. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.23.11183 · Cited by 474 · see citing works
Acceleration of Alzheimer's fibril formation by apolipoprotein E in vitro.
(1994) · PubMed Central · Cited by 441 · see citing works
Sanan, D. A., Weisgraber, K. H., Russell, S. J., Mahley, R. W., Huang, D., Saunders, A., Schmechel, D., Wisniewski, T., Frangione, B., & Roses, A. D. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117407 · Cited by 404 · see citing works
Self-citationButtini, M., Orth, M., Bellosta, S., Akeefe, H., Pitas, R. E., Wyss‐Coray, T., Mucke, L., & Mahley, R. W. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-12-04867.1999 · Cited by 361 · see citing works
Self-citationStraight and paired helical filaments in Alzheimer disease have a common structural unit.
Crowther, R. A. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.6.2288 · Cited by 354 · see citing works
Roses, A. D. (1994) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199409000-00002 · Cited by 329 · see citing works
Human apolipoprotein E: the Alzheimer's disease connection
Weisgraber, K. H., & Mahley, R. W. (1996) · The FASEB Journal · doi:10.1096/fasebj.10.13.8940294 · Cited by 327 · see citing works
Self-citationDong, L. M., Wilson, C., Wardell, M. R., Simmons, T., Mahley, R. W., Weisgraber, K. H., & Agard, D. A. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)31797-0 · Cited by 320 · see citing works
Self-citationHuman Apolipoprotein E4 Domain Interaction
Dong, L.-M., & Weisgraber, K. H. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.32.19053 · Cited by 318 · see citing works
Bellosta, S., Nathan, B. P., Orth, M., Dong, L.-M., Mahley, R. W., & Pitas, R. E. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.45.27063 · Cited by 313 · see citing works
Self-citationNathan, B. P., Chang, K.-C., Bellosta, S., Brisch, E., Ge, N., Mahley, R. W., & Pitas, R. E. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.34.19791 · Cited by 276 · see citing works
Self-citationNagy, Z. S., Esiri, M. M., Jobst, K. A., Johnston, C., Litchfield, S., Sim, E., & Smith, A. D. (1995) · Neuroscience · doi:10.1016/0306-4522(95)00331-c · Cited by 250 · see citing works
Tesseur, I. C., Dorpe, J. V., Spittaels, K., den Haute, C. V., Moechars, D., & LEUVEN, F. V. (2000) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64963-2 · Cited by 241 · see citing works
Human apolipoprotein E. Determination of the heparin binding sites of apolipoprotein E3.
Weisgraber, K. H., Rall, S. C., Mahley, R. W., Milne, R. W., Marcel, Y. L., & Sparrow, J. T. (1986) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)35898-2 · Cited by 240 · see citing works
Self-citationSmith, M. A., Rudnicka-Nawrot, M., Richey, P., Praprotnik, D., Mulvihill, P., Miller, C., Sayre, L., & Perry, G. (1995) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1995.64062660.x · Cited by 240 · see citing works
Han, S.-H., Einstein, G., Weisgraber, K. H., Strittmatter, W. J., Saunders, A. M., Pericak-Vance, M., Roses, A. D., & Schmechel, D. E. (1994) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199409000-00013 · Cited by 195 · see citing works
Apolipoprotein E localization in rat hepatocytes by immunogold labeling of cryothin sections
Hamilton, R., Wong, J., Guo, L., Krisans, S. K., & Havel, R. (1990) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)42343-0 · Cited by 152 · see citing works
Vickers, J. C., Riederer, B. M., Marugg, R. A., Buée‐Scherrer, V., Buée, L., Delacourte, A., & Morrison, J. H. (1994) · Neuroscience · doi:10.1016/0306-4522(94)90310-7 · Cited by 133 · see citing works
Stella, N., Pellerin, L., & Magistretti, P. J. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-05-03307.1995 · Cited by 80 · see citing works
Apolipoprotein E4 Promotes Incipient Alzheimer Pathology in the Elderly
Warzok, R., Kessler, C., Apel, G., Schwarz, A., Egensperger, R., Schreiber, D., Herbst, E. W., Wolf, E., Walther, R., & Walker, L. C. (1998) · Alzheimer Disease & Associated Disorders · doi:10.1097/00002093-199803000-00005 · Cited by 67 · see citing works
Immunocytochemical properties of Alzheimer straight filaments
Perry, G. L., Mulvihill, P., Manetto, V., et al. (1987) · Journal of Neuroscience · doi:10.1523/jneurosci.07-11-03736.1987 · Cited by 66 · see citing works
Alzheimer pathology of patients carrying apoliprotein E ε4 allele
Heinonen, O. (1995) · Neurobiology of Aging · doi:10.1016/0197-4580(95)00076-q · Cited by 52 · see citing works
Fiumelli, H., Jabaudon, D., Magistretti, P. J., & Martin, J. (1999) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.1999.00580.x · Cited by 51 · see citing works
Morris, C. M., Benjamin, R., Leake, A., McArthur, F. K., Candy, J. M., Ince, P. G., Torvik, A., Bjertness, E., & Edwardson, J. A. (1995) · Neuroscience Letters · doi:10.1016/0304-3940(94)12126-b · Cited by 38 · see citing works
The intracellular fate of apolipoprotein E is tau dependent and apoe allelespecific
Lovestone, S., Anderton, B. H., Hartley, C., Jensen, T. G., & Jørgensen, A. L. (1996) · Neuroreport · doi:10.1097/00001756-199604100-00010 · Cited by 35 · see citing works
Tau protein and paired helical filaments of Alzheimer's disease
Crowther, R. A. (1993) · Current Opinion in Structural Biology · doi:10.1016/s0959-440x(05)80153-8 · Cited by 32 · see citing works
März, W., Scharnagl, H., Kırça, M., Böhl, J., GROß, W., & Ohm, T. G. (1996) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1996.tb34432.x · Cited by 30 · see citing works
DeMattos, R. B., Thorngate, F. E., & Williams, D. L. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-07-02464.1999 · Cited by 30 · see citing works
Plasma Lipids and Their Role in Disease
(2003) · CRC Press eBooks · doi:10.1201/9781482298253 · Cited by 25 · see citing works
Mukaetova‐Ladinska, E. B., Harrington, C. R., Roth, M., & Wischik, C. M. (1997) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000106646 · Cited by 15 · see citing works
Macromolecular assemblages — putting the pieces together
Crowther, R. A., & Prasad, B. V. V. (2004) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2004.03.015 · Cited by 7 · see citing works
Apolipoprotein E and Human Disease
Huang, Y., & Mahley, R. W. (2010) · Taylor & Francis eBooks · doi:10.4324/9780203304815_chapter_13 · Cited by 6 · see citing works
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Masters, C. L., Bateman, R., Blennow, K., Rowe, C. C., Sperling, R. A., & Cummings, J. L. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.56 · Cited by 1,853 · see citing works
ApoE4 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 · see citing works
Mahley, R. W., Weisgraber, K. H., & Huang, Y. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0600549103 · Cited by 912 · see citing works
Self-citationApolipoprotein E: Structure and function in lipid metabolism, neurobiology, and Alzheimer’s diseases
Huang, Y., & Mahley, R. W. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.08.025 · Cited by 829 · see citing works
Self-citationApolipoprotein E: from cardiovascular disease to neurodegenerative disorders
Mahley, R. W. (2016) · Journal of Molecular Medicine · doi:10.1007/s00109-016-1427-y · Cited by 837 · see citing works
Self-citationRisner, 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 · see citing works
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 · see citing works
Interplay between innate immunity and Alzheimer disease: APOE and TREM2 in the spotlight
Shi, Y., & Holtzman, D. M. (2018) · Nature Reviews Immunology · doi:10.1038/s41577-018-0051-1 · Cited by 595 · see citing works
Amyloid cascade hypothesis: Pathogenesis and therapeutic strategies in Alzheimer's disease
Barage, S. H., & Sonawane, K. D. (2015) · Neuropeptides · doi:10.1016/j.npep.2015.06.008 · Cited by 579 · see citing works
Linking Aβ and Tau in Late-Onset Alzheimer's Disease: A Dual Pathway Hypothesis
Small, S. A., & Duff, K. (2008) · Neuron · doi:10.1016/j.neuron.2008.11.007 · Cited by 546 · see citing works
Central Nervous System Lipoproteins: ApoE and Regulation of Cholesterol Metabolism
Mahley, R. W. (2016) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.116.307023 · Cited by 516 · see citing works
Self-citationReelin, lipoprotein receptors and synaptic plasticity
Herz, J., & Chen, Y. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn2009 · Cited by 524 · see citing works
Xu, Q., Bernardo, A., Walker, D., Kanegawa, T., Mahley, R. W., & Huang, Y. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.5476-05.2006 · Cited by 524 · see citing works
Self-citationApolipoprotein 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 · see citing works
Self-citationBrecht, 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 · see citing works
Self-citationImpact of Apolipoprotein E (ApoE) Polymorphism on Brain ApoE Levels
Riddell, D. R., Zhou, H., Atchison, K., Warwick, H. K., Atkinson, P. J., Jefferson, J., Xu, L., Aschmies, S., Kirksey, Y., Hu, Y., et al. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.1972-08.2008 · Cited by 342 · see citing works
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 · see citing works
Self-citationAndrews-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 · see citing works
Self-citationChang, S., Ma, T. R., Miranda, R. D., Balestra, M. E., Mahley, R. W., & Huang, Y. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0508254102 · Cited by 319 · see citing works
Self-citationLi, G., Bien-Ly, N., Andrews-Zwilling, Y., Xu, Q., Bernardo, A., Ring, K., Halabisky, B., Deng, C., Mahley, R. W., & Huang, Y. (2009) · Cell Stem Cell · doi:10.1016/j.stem.2009.10.015 · Cited by 288 · see citing works
Self-citationApolipoprotein E ε4 allele, AD pathology, and the clinical expression of Alzheimer’s disease
Bennett, D. A., Wilson, R. S., Schneider, J. A., Evans, D. A., Aggarwal, N. T., Arnold, S. E., Cochran, E. J., Berry-Kravis, E., & Bienias, J. L. (2003) · Neurology · doi:10.1212/01.wnl.0000042478.08543.f7 · Cited by 282 · see citing works
Huang, Y., Weisgraber, K. H., Mucke, L., & Mahley, R. W. (2004) · Journal of Molecular Neuroscience · doi:10.1385/jmn:23:3:189 · Cited by 242 · see citing works
Self-citationApolipoprotein 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
Self-citationUddin, 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 · see citing works
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
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 · see citing works
Self-citationApolipoprotein E4 Forms a Molten Globule
Morrow, J. A., Hatters, D. M., Lu, B., Höchtl, P., Oberg, K. A., Rupp, B., & Weisgraber, K. H. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204898200 · Cited by 204 · see citing works
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 · see citing works
Self-citationSerrano‐Pozo, A., Qian, J., Monsell, S. E., Betensky, R. A., & Hyman, B. T. (2015) · Annals of Neurology · doi:10.1002/ana.24369 · Cited by 176 · see citing works
Buttini, M., Yu, G.-Q., Shockley, K., Huang, Y., Jones, B., Masliah, E., Mallory, M., Yeo, T., Longo, F. M., & Mucke, L. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-24-10539.2002 · Cited by 183 · see citing works
“ApoE levels in brain tissues were quantitated by Western blot analysis as described previously (Huang et al., 1996, 2001).”
BackgroundMethodJi, 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
Self-citationAβ-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
Self-citationApolipoprotein E and cholesterol in aging and disease in the brain
de Chaves, E. P., Narayanaswami, V., Christoffersen, C., & Nielsen, L. B. (2008) · Future Lipidology · doi:10.2217/17460875.3.5.505 · Cited by 164 · see citing works
More than cholesterol transporters: lipoprotein receptors in CNS function and neurodegeneration
Lane-Donovan, C., Philips, G. T., & Herz, J. (2014) · Neuron · doi:10.1016/j.neuron.2014.08.005 · Cited by 158 · see citing works
Pires, M., & Rego, A. C. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24010778 · Cited by 157 · see citing works
Harris, F. M., Brecht, W. J., Xu, Q., Mahley, R. W., & Huang, Y. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m408127200 · Cited by 151 · see citing works
Self-citationImpaired 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
Alzheimer's disease cerebrospinal fluid biomarker in cognitively normal subjects
Toledo, J. B., Zetterberg, H., van Harten, A. C., Glodzik, L., Martinez-Lage, P., Bocchio-Chiavetto, L., Rami, L., Hansson, O., Sperling, R., Engelborghs, S., et al. (2015) · Brain · doi:10.1093/brain/awv199 · Cited by 136 · see citing works
Nakamura, T., Watanabe, A., Fujino, T., Hosono, T., & Michikawa, M. (2009) · Molecular Neurodegeneration · doi:10.1186/1750-1326-4-35 · Cited by 124 · see citing works
Liraz, O., Boehm-Cagan, A., & Michaelson, D. M. (2013) · Molecular Neurodegeneration · doi:10.1186/1750-1326-8-16 · Cited by 118 · see citing works
Amino-terminal domain stability mediates apolipoprotein E aggregation into neurotoxic fibrils
Hatters, D. M., Zhong, N., Rutenber, E., & Weisgraber, K. H. (2006) · Journal of Molecular Biology · doi:10.1016/j.jmb.2006.06.080 · Cited by 105 · see citing works
Rousselet, E., Marcinkiewicz, J., Kriz, J., Zhou, A., Hatten, M. E., Prat, A., & Seidah, N. G. (2011) · Journal of Lipid Research · doi:10.1194/jlr.m014118 · Cited by 107 · see citing works
APOE alters glucose flux through central carbon pathways in astrocytes
Williams, H. C., Farmer, B. C., Piron, M. A., Walsh, A. E., Bruntz, R. C., Gentry, M. S., Sun, R. C., & Johnson, L. A. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104742 · Cited by 105 · see citing works
PICALM and Alzheimer’s Disease: An Update and Perspectives
Ando, K., Nagaraj, S., Küçükali, F., de Fisenne, M.-A., Kosa, A.-C., Doeraene, E., Lopez Gutierrez, L., Brion, J.-P., & Leroy, K. (2022) · Cells · doi:10.3390/cells11243994 · Cited by 104 · see citing works
Orr, A. L., Kim, C., Jimenez-Morales, D., Newton, B. W., Johnson, J. R., Krogan, N. J., Swaney, D. L., & Mahley, R. W. (2019) · Journal of Alzheimer's Disease · doi:10.3233/jad-181184 · Cited by 103 · see citing works
Self-citationInhibition 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
Characterization of the Heparin Binding Sites in Human Apolipoprotein E
Saito, H., Dhanasekaran, P., Nguyen, D., Baldwin, F., Weisgraber, K. H., Wehrli, S., Phillips, M. C., & Lund-Katz, S. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m213207200 · Cited by 90 · see citing works
Apolipoprotein E and Alzheimer's disease: the protective effects of ApoE2 and E3
Rebeck, G. W., Kindy, M., & LaDu, M. J. (2002) · Journal of Alzheimer's Disease · doi:10.3233/jad-2002-4304 · Cited by 89 · see citing works
Roses, A. D. (2006) · Journal of Alzheimer's Disease · doi:10.3233/jad-2006-9s340 · Cited by 86 · see citing works
Disentangling the effects of age and APOE on neuropathology and late life cognitive decline
Yu, L., Boyle, P. A., Leurgans, S., Schneider, J. A., & Bennett, D. A. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.10.074 · Cited by 71 · see citing works
Koch, G., Di Lorenzo, F., Loizzo, S., Motta, C., Travaglione, S., Baiula, M., Rimondini, R., Ponzo, V., Bonnì, S., Toniolo, S., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-14204-3 · Cited by 64 · 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
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
Apolipoprotein E: Remarkable Protein Sheds Light on Cardiovascular and Neurological Diseases
Mahley, R. W. (2017) · Clinical Chemistry · doi:10.1373/clinchem.2016.255695 · Cited by 53 · see citing works
Self-citationApolipoprotein 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 · see citing works
Effect of Carboxyl-Terminal Truncation on Structure and Lipid Interaction of Human Apolipoprotein E4
Tanaka, M., Vedhachalam, C., Sakamoto, T., Dhanasekaran, P., Phillips, M. C., Lund-Katz, S., & Saito, H. (2006) · Biochemistry · doi:10.1021/bi060023b · Cited by 43 · see citing works
An apolipoprotein E4 fragment can promote intracellular accumulation of amyloid peptide beta 42
Dafnis, I., Stratikos, E., Tzinia, A., Tsilibary, E. C., Zannis, V. I., & Chroni, A. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.06756.x · Cited by 41 · see citing works
The presence of apoE4, not the absence of apoE3, contributes to AD pathology
Teter, B., Raber, J., Nathan, B., & Crutcher, K. A. (2002) · Journal of Alzheimer's Disease · doi:10.3233/jad-2002-4305 · Cited by 37 · see citing works
Argyri, L., Dafnis, I., Theodossiou, T. A., Gantz, D., Stratikos, E., & Chroni, A. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.538124 · Cited by 30 · see citing works
Marques, M. A., Owens, P. A., & Crutcher, K. A. (2004) · Journal of Molecular Neuroscience · doi:10.1385/jmn:24:1:073 · Cited by 29 · see citing works
Fan, K., Francis, L., Aslam, M. M., Bedison, M. A., Lawrence, E., Acharya, V., Snitz, B. E., Ganguli, M., DeKosky, S. T., Lopez, O. L., et al. (2023) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2022.11.007 · Cited by 21 · see citing works
Gal, J., Katsumata, Y., Zhu, H., Srinivasan, S., Chen, J., Johnson, L. A., Wang, W.-X., Golden, L. R., Wilcock, D. M., Jicha, G. A., et al. (2022) · The American Journal of Pathology · doi:10.1016/j.ajpath.2021.11.013 · Cited by 17 · see citing works
Prasinou, P., Dafnis, I., Giacometti, G., Ferreri, C., Chroni, A., & Chatgilialoglu, C. (2017) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2017.07.001 · Cited by 15 · see citing works
- Authors
- Huang, Y., Liu, X. Q., Wyss-Coray, T., Brecht, W. J., Sanan, D. A., & Mahley, R. W.
- Affiliations
- University of California, San Francisco (US)
- Gladstone Institute of Neurological Disease and Gladstone Institute of Cardiovascular Disease, P.O. Box 419100, San Francisco, CA 94141-9100; and Departments of Pathology, Neurology, and Medicine, University of California, San Francisco, CA 94143
- Gladstone Institutes (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2001-07-10
- Volume
- 98
- Issue
- 15
- Pages
- 8838-8843
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC37522
- OpenAlex
- W2063505049
- Cited by
- 392
- References
- 48
- Citations by year
- 2026: 10 · 2025: 16 · 2024: 13 · 2023: 9 · 2022: 10 · 2021: 14 · 2020: 19 · 2019: 20 · 2018: 15 · 2017: 20 · 2016: 24 · 2015: 13 · 2014: 21 · 2013: 14 · 2012: 16
- FWCI
- 9.96
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › 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
- APOE ε4, Alzheimer's disease, neurofibrillary tangles, intracellular inclusions, tau phosphorylation, cytoskeletal interactions, APOE3, amyloid plaques
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Apolipoproteins E, Brain, Cells, Cultured, Inclusion Bodies, Cytosol, Humans, Intracellular Fluid, Neurons, Peptide Fragments, Mutagenesis, Neurofibrillary Tangles, tau Proteins, Neurofilament Proteins, Apolipoprotein E4
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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.
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