Reactivity of Apolipoprotein E4 and Amyloid β Peptide

Ji, Zhong-Sheng; Müllendorff, Karin; Cheng, Irene H.; Miranda, R. Dennis; Huang, Yadong; Mahley, Robert W.

doi:10.1074/jbc.m506646200

Cited by 127Alzheimer's disease research and treatmentsLysosomal Storage Disorders ResearchNeuroinflammation and Neurodegeneration Mechanisms

Reactivity of Apolipoprotein E4 and Amyloid β Peptide

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Ji, Zhong-Sheng, Müllendorff, Karin, Cheng, Irene H., Miranda, R. Dennis, Huang, Yadong, Mahley, Robert W.·2006·Journal of Biological Chemistry

DOI 10.1074/jbc.m506646200

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Abstract

We previously demonstrated that apolipoprotein E4 (apoE4) potentiates lysosomal leakage and apoptosis induced by amyloid beta (Abeta) peptide in cultured Neuro-2a cells and hypothesized that the low pH of lysosomes accentuates the conversion of apoE4 to a molten globule, inducing reactive intermediates capable of destabilizing cellular membranes. Here we report that neutralizing lysosomal pH with bafilomycin or NH4Cl abolished the apoE4 potentiation of Abeta-induced lysosomal leakage and apoptosis in Neuro-2a cells. Consistent with these results, apoE4 at acidic pH bound more avidly to phospholipid vesicles and disrupted them to a greater extent than at pH 7.4. Comparison of "Arctic" mutant Abeta, which forms multimers, and GM6 mutant Abeta, which remains primarily monomeric, showed that aggregation is essential for apoE4 to potentiate Abeta-induced lysosomal leakage and apoptosis. Both apoE4 and Abeta1-42 had to be internalized to exert these effects. Blocking the low density lipoprotein receptor-related protein with small interfering RNA abolished the enhanced effects of apoE4 and Abeta on lysosomes and apoptosis. In cultured Neuro-2a cells, Abeta1-42 increased lysosome formation to a greater extent in apoE3- or apoE4-transfected cells than in Neo-transfected cells, as shown by immunostaining for lysosome-associated membrane protein 1. Similarly, in transgenic mice expressing apoE and amyloid precursor protein, hippocampal neurons displayed increased numbers of lysosomes. Thus, apoE4 and Abeta1-42 may work in concert in neurons to increase lysosome formation while increasing the susceptibility of lysosomal membranes to disruption, release of lysosomal enzymes into the cytosol, and neuronal degeneration.

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The role of autophagy in neurodegenerative disease
Nixon, R. A. (2013) · Nature Medicine · doi:10.1038/nm.3232 · Cited by 2,059 · see citing works
Apolipoprotein E4: A causative factor and therapeutic target in neuropathology, including Alzheimer’s disease
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
Autophagy failure in Alzheimer's disease—locating the primary defect
Nixon, R. A., & Yang, D. (2011) · Neurobiology of Disease · doi:10.1016/j.nbd.2011.01.021 · Cited by 634 · 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
Apolipoprotein E: structure determines function, from atherosclerosis to Alzheimer's disease to AIDS
Mahley, R. W., Weisgraber, K. H., & Huang, Y. (2009) · Journal of Lipid Research · doi:10.1194/jlr.r800069-jlr200 · Cited by 580 · see citing works
Disorders of lysosomal acidification—The emerging role of v-ATPase in aging and neurodegenerative disease
Colacurcio, D. J., & Nixon, R. A. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.05.004 · Cited by 548 · see citing works
Regulation of apoptosis-associated lysosomal membrane permeabilization
Johansson, A., Appelqvist, H., Nilsson, C., Kågedal, K., Roberg, K. B., & Öllinger, K. M. (2010) · APOPTOSIS · doi:10.1007/s10495-009-0452-5 · Cited by 463 · see citing works
Amyloid precursor protein and endosomal-lysosomal dysfunction in Alzheimer's disease: inseparable partners in a multifactorial disease
Nixon, R. A. (2017) · The FASEB Journal · doi:10.1096/fj.201700359 · Cited by 400 · see citing works
Accelerating Amyloid-β Fibrillization Reduces Oligomer Levels and Functional Deficits in Alzheimer Disease Mouse Models
Cheng, I. H.-J., Scearce-Levie, K. A., Legleiter, J. A., Palop, J. J., Gerstein, H., Bien‐Ly, N., Puolivaöli, J., Lesné, S., Ashe, K. H., Muchowski, P. J., et al. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m701078200 · Cited by 403 · see citing works
Evolution of the human lifespan and diseases of aging: Roles of infection, inflammation, and nutrition
Finch, C. E. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909606106 · Cited by 407 · see citing works
Neurodegenerative lysosomal disorders: A continuum from development to late age
Nixon, R. A., Yang, D.-S., & Lee, J.-H. (2008) · Autophagy · doi:10.4161/auto.6259 · Cited by 362 · see citing works
Membrane and surface interactions of Alzheimer’s Aβ peptide – insights into the mechanism of cytotoxicity
Williams, T. L., & Serpell, L. C. (2011) · FEBS Journal · doi:10.1111/j.1742-4658.2011.08228.x · Cited by 335 · see citing works
Autophagy and Alzheimer’s Disease
Li, Q., Liu, Y., & Sun, M. (2016) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-016-0386-8 · Cited by 331 · see citing works
Autophagy in neurodegenerative disease: friend, foe or turncoat?
Nixon, R. A. (2006) · Trends in Neurosciences · doi:10.1016/j.tins.2006.07.003 · Cited by 315 · see citing works
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 · see citing works
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 · see citing works
Clearance of cerebral Aβ in Alzheimer’s disease: reassessing the role of microglia and monocytes
Zuroff, L. R., Daley, D. A., Black, K. L., & Koronyo‐Hamaoui, M. (2017) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-017-2463-7 · Cited by 275 · see citing works
The biological pathways of Alzheimer disease: a review
Calabrò, M., Rinaldi, C., Santoro, G., & Crisafulli, C. (2020) · AIMS neuroscience · doi:10.3934/neuroscience.2021005 · Cited by 271 · see citing works
Disease-Associated Prion Protein Oligomers Inhibit the 26S Proteasome
Kristiansen, M., Deriziotis, P., Dimcheff, D. E., Jackson, G. S., Ovaa, H., Naumann, H., Clarke, A. R., van Leeuwen, F. W. B., Menéndez-Benito, V., Dantuma, N. P., et al. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.04.001 · Cited by 262 · see citing works
Hallmarks of Aging: An Autophagic Perspective
Barbosa, M. C., Grosso, R. A., & Fader, C. M. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00790 · Cited by 265 · see citing works
Autophagy Induction as a Therapeutic Strategy for Neurodegenerative Diseases
Djajadikerta, A., Keshri, S., Tanasa, M. P., Prestil, R., Ryan, L., & Rubinsztein, D. C. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.12.035 · Cited by 238 · see citing works
Detection and Clearance of Damaged Lysosomes by the Endo-Lysosomal Damage Response and Lysophagy
Papadopoulos, C., & Meyer, H. (2017) · Current Biology · doi:10.1016/j.cub.2017.11.012 · Cited by 230 · see citing works
The Genetic Variability of APOE in Different Human Populations and Its Implications for Longevity
Abondio, P., Sazzini, M., Garagnani, P., Boattini, A., Monti, D., Franceschi, C., Luiselli, D., & Giuliani, C. (2019) · Genes · doi:10.3390/genes10030222 · Cited by 226 · see citing works
Endo-lysosomal dysregulations and late-onset Alzheimer’s disease: impact of genetic risk factors
Van Acker, Z. P., Bretou, M., & Annaert, W. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0323-7 · Cited by 222 · see citing works
Neuronal Mitophagy in Neurodegenerative Diseases
Martínez‐Vicente, M. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00064 · Cited by 216 · see citing works
Cross-Talk between Apolipoprotein E and Cytokines
Zhang, H., Wu, L., & Wu, J. (2011) · Mediators of Inflammation · doi:10.1155/2011/949072 · Cited by 199 · see citing works
The Ubiquitin-Proteasome System and the Autophagic-Lysosomal System in Alzheimer Disease
Ihara, Y., Morishima-Kawashima, M., & Nixon, R. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006361 · Cited by 190 · see citing works
Autophagy and Neuronal Cell Death in Neurological DisordersPreprint
Nixon, R. A., & Yang, D.-S. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a008839 · Cited by 179 · see citing works
ATP13A2 regulates mitochondrial bioenergetics through macroautophagy
Gusdon, A. M., Zhu, J., Van Houten, B., & Chu, C. T. (2012) · Neurobiology of Disease · doi:10.1016/j.nbd.2011.12.015 · Cited by 167 · see citing works
Apolipoprotein 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
Targeting Autophagy for the Treatment of Alzheimer’s Disease: Challenges and Opportunities
Liu, J., & Li, L. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00203 · Cited by 159 · see citing works
Accelerated age-related cortical thinning in healthy carriers of apolipoprotein E ɛ4
Espeseth, T., Westlye, L. T., Fjell, A. M., Walhovd, K. B., Rootwelt, H., & Reinvang, I. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2006.10.030 · Cited by 138 · see citing works
Mitochondrial Dysfunction in Alzheimer’s Disease: A Biomarker of the Future?
Bell, S., Barnes, K., Marco, M. D., Shaw, P. J., Ferraiuolo, L., Blackburn, D. J., Venneri, A., & Mortiboys, H. (2021) · Biomedicines · doi:10.3390/biomedicines9010063 · Cited by 136 · see citing works
The E693Δ Mutation in Amyloid Precursor Protein Increases Intracellular Accumulation of Amyloid β Oligomers and Causes Endoplasmic Reticulum Stress-Induced Apoptosis in Cultured Cells
Nishitsuji, K., Tomiyama, T., Ishibashi, K., Ito, K., Teraoka, R., Lambert, M. P., Klein, W. L., & Mori, H. (2009) · The American Journal of Pathology · doi:10.2353/ajpath.2009.080480 · Cited by 127 · see citing works
Genetic architecture of Alzheimer's disease
Neuner, S. M., TCW, J., & Goate, A. M. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104976 · Cited by 126 · see citing works
“In the context of the central nervous system, APOE ε4 has been linked to impaired Aβ clearance (Castellano et al., 2011; Wildsmith et al., 2013), disruption of lysosomes and neuronal apoptosis (Ji et al., 2002; Ji et al., 2006), as well as mitochondrial dysfunction (Chang et al., 2005).”
Background
Low-Density Lipoprotein Receptor-Related Protein 1 (LRP1) Mediates Neuronal Aβ42 Uptake and Lysosomal Trafficking
Fuentealba, R. A., Liu, Q., Zhang, J., Kanekiyo, T., Hu, X., Lee, J.-M., LaDu, M. J., & Bu, G. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011884 · Cited by 116 · see citing works
Autophagy in neurodegenerative diseases: From pathogenic dysfunction to therapeutic modulation
Martínez‐Vicente, M. (2015) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2015.03.005 · Cited by 109 · see citing works
Reconsider Alzheimer's disease by the ‘calpain–cathepsin hypothesis’—A perspective review
Yamashima, T. (2013) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.02.004 · Cited by 107 · see citing works
Activation of the amyloid cascade in apolipoprotein E4 transgenic mice induces lysosomal activation and neurodegeneration resulting in marked cognitive deficits
Belinson, H., Lev, D., Masliah, E., & Michaelson, D. M. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.5633-07.2008 · Cited by 101 · see citing works
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 97 · see citing works
The emerging roles of protein homeostasis‐governing pathways in Alzheimer's disease
Cheng, J., North, B. J., Zhang, T., Dai, X., Tao, K., Guo, J., & Wei, W. (2018) · Aging Cell · doi:10.1111/acel.12801 · Cited by 96 · see citing works
Interplay Between Mitochondrial Oxidative Disorders and Proteostasis in Alzheimer’s Disease
Llanos-González, E., Henares-Chavarino, Á. A., Pedrero-Prieto, C., García-Carpintero, S., Frontiñán-Rubio, J., Sancho-Bielsa, F., Alcaín, F. J., Peinado, J., Rabanal-Ruiz, Y., & Durán-Prado, M. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.01444 · Cited by 83 · see citing works
Environmental enrichment stimulates neurogenesis in apolipoprotein E3 and neuronal apoptosis in apolipoprotein E4 transgenic mice
Levi, O., & Michaelson, D. M. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04189.x · Cited by 94 · see citing works
Aβ Internalization by Neurons and Glia
Mohamed, A., & Chaves, E. (2011) · International Journal of Alzheimer s Disease · doi:10.4061/2011/127984 · Cited by 91 · see citing works
Cathepsin D-mediated proteolysis of apolipoprotein E: Possible role in Alzheimer’s disease
Zhou, W., Scott, S. A., Shelton, S. B., & Crutcher, K. A. (2006) · Neuroscience · doi:10.1016/j.neuroscience.2006.08.019 · Cited by 82 · see citing works
Preserving Lysosomal Function in the Aging Brain: Insights from Neurodegeneration
Peng, W., Minakaki, G., Nguyen, M., & Krainc, D. (2019) · Neurotherapeutics · doi:10.1007/s13311-019-00742-3 · Cited by 79 · see citing works
Sex Differences in Autophagy Contribute to Female Vulnerability in Alzheimer's Disease
Congdon, E. E. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00372 · Cited by 81 · see citing works
Protecting cells by protecting their vulnerable lysosomes: Identification of a new mechanism for preserving lysosomal functional integrity upon oxidative stress
Pascua‐Maestro, R., Diez‐Hermano, S., Lillo, C., Ganfornina, M. D., & Sánchez, D. (2017) · PLoS Genetics · doi:10.1371/journal.pgen.1006603 · Cited by 78 · see citing works
Oxidative stress induces macroautophagy of amyloid β-protein and ensuing apoptosis
Zheng, L. P., Kågedal, K., Dehvari, N., Benedikz, E., Cowburn, R. F., Marcusson, J. O., & Terman, A. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.10.043 · Cited by 73 · see citing works
The role of lysosome in cell death regulation
Yu, F., Chen, Z., Wang, B., Zhao, J., Hou, Y., Ma, S., & Liu, X. (2015) · Tumor Biology · doi:10.1007/s13277-015-4516-6 · Cited by 72 · see citing works
Autophagy Modulation as a Treatment of Amyloid Diseases
Mputhia, Z., Hone, E., Tripathi, T., Sargeant, T. J., Martins, R. N., & Bharadwaj, P. (2019) · Molecules · doi:10.3390/molecules24183372 · Cited by 69 · see citing works
Infection and Alzheimer's Disease: The APOE ε4 Connection and Lipid Metabolism
Urosevic, N., & Martins, R. N. (2008) · Journal of Alzheimer s Disease · doi:10.3233/jad-2008-13407 · Cited by 68 · see citing works
The generation and function of soluble apoE receptors in the CNS
Rebeck, G. W., LaDu, M. J., Estus, S., Bu, G., & Weeber, E. J. (2006) · Molecular Neurodegeneration · doi:10.1186/1750-1326-1-15 · Cited by 66 · see citing works
Trilateral association of autophagy, mTOR and Alzheimer’s disease: Potential pathway in the development for Alzheimer’s disease therapy
Subramanian, A., Tamilanban, T., Alsayari, A., Ramachawolran, G., Wong, L. S., Sekar, M., Gan, S. H., Subramaniyan, V., Chinni, S. V., Rani, N. N. I. M., et al. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.1094351 · Cited by 67 · see citing works
Primate aging in the mammalian scheme: the puzzle of extreme variation in brain aging
Finch, C. E., & Austad, S. N. (2012) · AGE · doi:10.1007/s11357-011-9355-9 · Cited by 68 · see citing works
Membrane Localization of β-Amyloid 1–42 in Lysosomes
Liu, R., Zhou, Q., Ji, S., Zhou, Q., Feng, D., Wu, Y., & Sui, S. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.036798 · Cited by 64 · see citing works
The p53 Core Domain Is a Molten Globule at Low pH
Bom, A. P. D. A., de Freitas, M. S., Moreira, F. S., Ferraz, D., Sanches, D., Gomes, A. M. O., Valente, A. P., Cordeiro, Y., & Silva, J. L. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.075861 · Cited by 61 · see citing works
Pharmacological modulation of autophagy for Alzheimer's disease therapy: Opportunities and obstacles
Deng, Z., Dong, Y., Zhou, X., Lu, J.-H., & Yue, Z. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2021.12.009 · Cited by 58 · see citing works
The Implications of Autophagy in Alzheimer’s Disease
Hamano, T., Hayashi, K., Shirafuji, N., & Nakamoto, Y. (2018) · Current Alzheimer Research · doi:10.2174/1567205015666181004143432 · Cited by 57 · see citing works
The lysosomal storage disease continuum with ageing-related neurodegenerative disease
Lloyd‐Evans, E., & Haslett, L. J. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.07.005 · Cited by 57 · see citing works
Cognitive decline and brain pathology in aging – need for a dimensional, lifespan and systems vulnerability view
Walhovd, K. B., Fjell, A. M., & Espeseth, T. (2014) · Scandinavian Journal of Psychology · doi:10.1111/sjop.12120 · Cited by 54 · see citing works
Contributions of the Carboxyl-Terminal Helical Segment to the Self-Association and Lipoprotein Preferences of Human Apolipoprotein E3 and E4 Isoforms
Sakamoto, T., Tanaka, M., Vedhachalam, C., Nickel, M., Nguyen, D., Dhanasekaran, P., Phillips, M. C., Lund-Katz, S., & Saito, H. (2008) · Biochemistry · doi:10.1021/bi701923h · Cited by 54 · see citing works
Aging-Dependent Mitophagy Dysfunction in Alzheimer’s Disease
Song, M., Zhao, X., & Song, F. (2021) · Molecular Neurobiology · doi:10.1007/s12035-020-02248-y · Cited by 56 · see citing works
Adaptation of neuronal cells to chronic oxidative stress is associated with altered cholesterol and sphingolipid homeostasis and lysosomal function
Clement, A. B., Gamerdinger, M., Tamboli, I. Y., Lütjohann, D., Walter, J., Greeve, I., Gimpl, G., & Behl, C. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06360.x · Cited by 53 · see citing works
Alzheimer's disease genes and autophagy
Yoon, S., & Kim, D. (2016) · Brain Research · doi:10.1016/j.brainres.2016.03.018 · Cited by 47 · see citing works
Targeting ApoE4/ApoE receptor LRP1 in Alzheimer's disease
Martiskainen, H., Haapasalo, A., Kurkinen, K. M. A., Pihlajamäki, J., Soininen, H. S., & Hiltunen, M. O. (2013) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2013.789862 · Cited by 45 · see citing works
Function and Comorbidities of Apolipoprotein E in Alzheimer′s Disease
Leduc, V., Domenger, D., Beaumont, L. D., Lalonde, D., Jasmin, S. B., & Poirier, J. (2011) · International Journal of Alzheimer s Disease · doi:10.4061/2011/974361 · Cited by 45 · see citing works
Calcium Ions Aggravate Alzheimer’s Disease Through the Aberrant Activation of Neuronal Networks, Leading to Synaptic and Cognitive Deficits
Guan, P.-P., Cao, L., Yang, Y., & Wang, P. (2021) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2021.757515 · Cited by 44 · see citing works
Apolipoprotein E4 Elicits Lysosomal Cathepsin D Release, Decreased Thioredoxin-1 Levels, and Apoptosis
Persson, T., Lattanzio, F., Calvo‐Garrido, J., Rimondini, R., Rubio-Rodrigo, M., Sundström, E., Maioli, S., Matton, A., & Cedazo-Mı́nguez, Á. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-150738 · Cited by 41 · see citing works
Apoptosis induces neuronal apolipoprotein-E synthesis and localization in apoptotic bodies
Elliott, D. A., Kim, W. S., Jans, D. A., & Garner, B. (2007) · Neuroscience Letters · doi:10.1016/j.neulet.2007.02.014 · Cited by 41 · see citing works
Amyloid-Related Memory Decline in Preclinical Alzheimer’s Disease Is Dependent on APOE ε4 and Is Detectable over 18-Months
Thai, C., Lim, Y. Y., Villemagne, V. L., Laws, S. M., Ames, D. J., Ellis, K. A., Rainey‐Smith, S. R., Martins, R. N., Masters, C. L., Rowe, C. C., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0139082 · Cited by 39 · see citing works
Molecular Mechanism of Autophagy: Its Role in the Therapy of Alzheimer’s Disease
Zhao, Y., Zhang, Y., Zhang, J., Zhang, X., & Yang, G. (2020) · Current Neuropharmacology · doi:10.2174/1570159x18666200114163636 · Cited by 40 · see citing works
Oxidative Stress in the Pathogenesis of Alzheimer's Disease and Cerebrovascular Disease with Therapeutic Implications
Jurcău, A., & Simion, A. (2020) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527319666200303121016 · Cited by 38 · see citing works
Activate or Inhibit? Implications of Autophagy Modulation as a Therapeutic Strategy for Alzheimer’s Disease
Krishnan, S., Shrestha, Y., Jayatunga, D. P. W., Rea, S. L., Martins, R. N., & Bharadwaj, P. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186739 · Cited by 37 · see citing works
The Interplay Between Apolipoprotein E4 and the Autophagic–Endocytic–Lysosomal Axis
Schmukler, E., Michaelson, D. M., & Pinkas-Kramarski, R. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-0892-4 · Cited by 35 · see citing works
Exploring the Mechanisms and Therapeutic Approaches of Mitochondrial Dysfunction in Alzheimer’s Disease: An Educational Literature Review
Moawad, M. H. E. D., Serag, I., Alkhawaldeh, I. M., Abbas, A., Sharaf, A., Alsalah, S., Sadeq, M. A., Shalaby, M. M. M., Hefnawy, M. T., Abouzid, M., et al. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-04468-y · Cited by 34 · see citing works
Arsenic induces apoptosis by the lysosomal‐mitochondrial pathway in INS‐1 cells
Pan, X., Jiang, L., Zhong, L., Geng, C., Li, J., Liu, S., Guan, H., Yang, G., Yao, X., Piao, F., et al. (2014) · Environmental Toxicology · doi:10.1002/tox.22027 · Cited by 34 · see citing works
A role for p53 in the β-amyloid-mediated regulation of the lysosomal system
Fogarty, M. P., McCormack, R. M., Noonan, J., Murphy, D. B., Gowran, A., & Campbell, V. A. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2008.09.018 · Cited by 34 · see citing works
APOE4 genetic polymorphism results in impaired recovery in a repeated mild traumatic brain injury model and treatment with Bryostatin-1 improves outcomes
Giarratana, A. O., Zheng, C., Reddi, S., Teng, S. L., Berger, D. S., Adler, D., Sullivan, P. M., Thakker‐Varia, S., & Alder, J. (2020) · Scientific Reports · doi:10.1038/s41598-020-76849-x · Cited by 33 · see citing works
Human APOE genotype affects intraneuronal A 1-42 accumulation in a lentiviral gene transfer model
Zhao, W., Dumanis, S. B., Tamboli, I. Y., Rodriguez, G. A., Jo LaDu, M., Moussa, C. E. H., & William Rebeck, G. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddt525 · Cited by 32 · see citing works
Apolipoprotein E ε4-related thickening of the cerebral cortex modulates selective attention
Espeseth, T., Westlye, L. T., Walhovd, K. B., Fjell, A. M., Endestad, T., Rootwelt, H., & Reinvang, I. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2009.12.027 · Cited by 32 · see citing works
Prions and the proteasome
Deriziotis, P., & Tabrizi, S. J. (2008) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2008.06.011 · Cited by 29 · see citing works
Quantitative Microproteomics Based Characterization of the Central and Peripheral Nervous System of a Mouse Model of Krabbe Disease
Pellegrini, D., Grosso, A. D., Angella, L., Giordano, N. C., Dilillo, M., Tonazzini, I., Caleo, M., Cecchini, M. G., & McDonnell, L. A. (2019) · Molecular & Cellular Proteomics · doi:10.1074/mcp.ra118.001267 · Cited by 27 · see citing works
Endosomal‐lysosomal dysfunctions in Alzheimer’s disease: Pathogenesis and therapeutic interventions
Lai, S. S. M., Ng, K. Y., Koh, R. Y., Chok, K. C., & Chye, S. M. (2021) · Metabolic Brain Disease · doi:10.1007/s11011-021-00737-0 · Cited by 28 · see citing works
Self-Association and Stability of the ApoE Isoforms at Low pH: Implications for ApoE–Lipid Interactions
Garai, K., Baban, B. A., & Frieden, C. (2011) · Biochemistry · doi:10.1021/bi2006702 · Cited by 26 · see citing works
UsingDrosophilaModels of Amyloid Toxicity to Study Autophagy in the Pathogenesis of Alzheimer’s Disease
O’Keefe, L. V., & Denton, D. (2018) · BioMed Research International · doi:10.1155/2018/5195416 · Cited by 24 · see citing works
Human APOE4 Protects High-Fat and High-Sucrose Diet Fed Targeted Replacement Mice against Fatty Liver Disease Compared to APOE3
Huebbe, P., Bilke, S., Rueter, J., Schloesser, A., Campbel, G., Glüer, C.-C., Lucius, R., Röcken, C., Tholey, A., & Rimbach, G. (2024) · Aging and disease · doi:10.14336/ad.2023.0530 · Cited by 24 · see citing works
Transmissible Endosomal Intoxication: A Balance between Exosomes and Lysosomes at the Basis of Intercellular Amyloid Propagation
Bécot, A., Volgers, C., & van Niel, G. (2020) · Biomedicines · doi:10.3390/biomedicines8080272 · Cited by 24 · see citing works
Knockdown of Parkinson’s disease-related gene ATP13A2 reduces tumorigenesis via blocking autophagic flux in colon cancer
Chen, Q., Li, Z., Zhou, C., Feng, Y., Liu, Q., Zhou, D., Lu, X., Du, G.-S., Jian, D., Luo, H., et al. (2020) · Cell & Bioscience · doi:10.1186/s13578-020-00506-z · Cited by 24 · see citing works
GTP energy dependence of endocytosis and autophagy in the aging brain and Alzheimer’s disease
Santana-Martínez, R. A., Pinky, P. D., Harlan, B. A., & Brewer, G. J. (2023) · GeroScience · doi:10.1007/s11357-022-00717-x · Cited by 24 · see citing works
Inhibiting Autophagy Pathway of PI3K/AKT/mTOR Promotes Apoptosis in SK-N-SH Cell Model of Alzheimer’s Disease
Pang, Y., Lin, W., Zhan, L., Zhang, J., Zhang, S., Jin, H., Zhang, H., Wang, X., & Li, X. (2022) · Journal of Healthcare Engineering · doi:10.1155/2022/6069682 · Cited by 20 · see citing works
Retracted
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Pathological Synergism Between Amyloid-β and Apolipoprotein E4 – The Most Prevalent Yet Understudied Genetic Risk Factor for Alzheimer's Disease
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Apolipoprotein E4 Potentiates Amyloid β Peptide-induced Lysosomal Leakage and Apoptosis in Neuronal Cells
Ji, Z.-S., Miranda, R. D., Newhouse, Y. M., Weisgraber, K. H., Huang, Y., & Mahley, R. W. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m112109200 · Cited by 177 · see citing works
An apolipoprotein E4 fragment can promote intracellular accumulation of amyloid peptide beta 42
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Authors: Ji, Z.-S., Müllendorff, K., Cheng, I. H., Miranda, R. D., Huang, Y., & Mahley, R. W.
Affiliations: University of California, San Francisco (US)
Corresponding author: Mahley, Robert W.
ORCID: Cheng, Irene H.
Huang, Yadong
Mahley, Robert W.
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 2006-02
Volume: 281
Issue: 5
Pages: 2683-2692
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.m506646200
OpenAlex: W2048371394
Cited by: 127
References: 78
Citations by year: 2026: 2 · 2025: 3 · 2024: 5 · 2023: 1 · 2022: 7 · 2021: 6 · 2020: 12 · 2019: 9 · 2018: 6 · 2017: 7 · 2016: 9 · 2015: 3 · 2014: 2 · 2013: 5 · 2012: 6
FWCI: 4.59
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 5359 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: National Institutes of Health (1c06rr018928-01)
National Institute on Aging (P01AG022074)
National Institute of Neurological Disorders and Stroke (R21NS046465)
National Center for Research Resources (C06RR18928)
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: APOE ε4, amyloid-beta, apoptosis, lysosomal pH, molten globule, lysosomal membrane disruption, amyloid fibril formation, amyloid-beta 42, low density lipoprotein receptor-related protein, lysosome-associated membrane protein 1, lysosome formation, hippocampal neurons, Alzheimer's disease, N2a cells
MeSH terms: Animals, Apolipoproteins E, Cell Line, Humans, Hydrogen-Ion Concentration, Intracellular Membranes, Liposomes, Lysosomes, Mice, Transgenic, Neurons, Transfection, Amyloid beta-Peptides, Apoptosis, Dimerization, Neurodegenerative Diseases, Mice, Apolipoprotein E4

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Reactivity of Apolipoprotein E4 and Amyloid β Peptide

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