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High‐density lipoprotein mimetic peptide 4F mitigates amyloid‐β‐induced inhibition of apolipoprotein E secretion and lipidation in primary astrocytes and microglia
Abstract
The apolipoprotein E (apoE) ε4 allele is the primary genetic risk factor for late‐onset Alzheimer's disease (AD). ApoE in the brain is produced primarily by astrocytes; once secreted from these cells, apoE binds lipids and forms high‐density lipoprotein (HDL)‐like particles. Accumulation of amyloid‐β protein (Aβ) in the brain is a key hallmark of AD, and is thought to initiate a pathogenic cascade leading to neurodegeneration and dementia. The level and lipidation state of apoE affect Aβ aggregation and clearance pathways. Elevated levels of plasma HDL are associated with lower risk and severity of AD; the underlying mechanisms, however, have not been fully elucidated. This study was designed to investigate the impact of an HDL mimetic peptide, 4F, on the secretion and lipidation of apoE. We found that 4F significantly increases apoE secretion and lipidation in primary human astrocytes as well as in primary mouse astrocytes and microglia. Aggregated Aβ inhibits glial apoE secretion and lipidation, causing accumulation of intracellular apoE, an effect that is counteracted by co‐treatment with 4F. Pharmacological and gene editing approaches show that 4F mediates its effects partially through the secretory pathway from the endoplasmic reticulum to the Golgi apparatus and requires the lipid transporter ATP‐binding cassette transporter A1. We conclude that the HDL mimetic peptide 4F promotes glial apoE secretion and lipidation and mitigates the detrimental effects of Aβ on proper cellular trafficking and functionality of apoE. These findings suggest that treatment with such an HDL mimetic peptide may provide therapeutic benefit in AD. image Read the Editorial Highlight for this article on page 580.
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ApoE4 lipoproteins in the brain and in CSF are hypolipidated.
“ApoE4 lipoproteins in the brain and in CSF are hypolipidated (Hu et al., 2015;Heinsinger et al., 2016;Chernick et al., 2018).”
From ApoE4 Alters ABCA1 Membrane Trafficking in Astrocytes (2019) · cites this paper as Chernick et al., 2018
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Krasemann, S., Madore, C., Cialic, R., Baufeld, C., Calcagno, N., El Fatimy, R., Beckers, L., O’Loughlin, E., Xu, Y., Fanek, Z., et al. (2017) · Immunity · doi:10.1016/j.immuni.2017.08.008 · Cited by 2,979
Alzheimer disease in the United States (2010–2050) estimated using the 2010 census
Hebert, L. E., Weuve, J., Scherr, P. A., & Evans, D. A. (2013) · Neurology · doi:10.1212/wnl.0b013e31828726f5 · Cited by 2,642
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
Apolipoprotein E and its receptors in Alzheimer's disease: pathways, pathogenesis and therapy
Bu, G. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2620 · Cited by 1,168
ApoE-Directed Therapeutics Rapidly Clear β-Amyloid and Reverse Deficits in AD Mouse Models
Cramer, P. E., Cirrito, J. R., Wesson, D. W., Lee, C. Y. D., Karlo, J. C., Zinn, A. E., Casali, B. T., Restivo, J. L., Goebel, W. D., James, M. J., et al. (2012) · Science · doi:10.1126/science.1217697 · Cited by 1,050
Yeh, F. L., Wang, Y., Tom, I., Gonzalez, L. C., & Sheng, M. (2016) · Neuron · doi:10.1016/j.neuron.2016.06.015 · Cited by 943
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
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
Apolipoprotein E and Apolipoprotein E Receptors: Normal Biology and Roles in Alzheimer Disease
Holtzman, D. M., Herz, J., & Bu, G. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006312 · Cited by 782
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
Apolipoprotein E Is a Ligand for Triggering Receptor Expressed on Myeloid Cells 2 (TREM2)
Atagi, Y., Liu, C.-C., Painter, M. M., Chen, X.-F., Verbeeck, C., Zheng, H., Li, X., Rademakers, R., Kang, S. S., Xu, H., et al. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.679043 · Cited by 587
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
Preparing Synthetic Aβ in Different Aggregation States
Stine, W. B., Jungbauer, L., Yu, C., & LaDu, M. J. (2010) · Methods in Molecular Biology · doi:10.1007/978-1-60761-744-0_2 · Cited by 403
Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease
Wahrle, S. E., Jiang, H., Parsadanian, M., Kim, J., Li, A., Knoten, A., Jain, S., Hirsch-Reinshagen, V., Wellington, C. L., Bales, K. R., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci33622 · Cited by 370
Lack of ABCA1 Considerably Decreases Brain ApoE Level and Increases Amyloid Deposition in APP23 Mice
Koldamova, R., Staufenbiel, M., & Lefterov, I. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m504513200 · Cited by 350
The Triggering Receptor Expressed on Myeloid Cells 2 Binds Apolipoprotein E
Bailey, C. C., DeVaux, L. B., & Farzan, M. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.677286 · Cited by 303
Hirsch-Reinshagen, V., Maia, L. F., Burgess, B. L., Blain, J.-F., Naus, K. E., McIsaac, S. A., Parkinson, P. F., Chan, J. Y., Tansley, G. H., Hayden, M. R., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m508781200 · Cited by 233
APOE genotype alters glial activation and loss of synaptic markers in mice
Zhu, Y., Nwabuisi‐Heath, E., Dumanis, S. B., Tai, L. M., Yu, C., Rebeck, G. W., & Ladu, M. J. (2012) · Glia · doi:10.1002/glia.22289 · Cited by 224
Self-citationFagan, A. M., Holtzman, D. M., Munson, G., Mathur, T., Schneider, D., Chang, L. K., Getz, G. S., Reardon, C. A., Lukens, J., Shah, J. A., et al. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.42.30001 · Cited by 222
Apolipoprotein E metabolism and functions in brain and its role in Alzheimer's disease
Liao, F., Yoon, H., & Kim, J. (2017) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000383 · Cited by 191 · cited 1×
“It has been shown that apoE interacts with Ab and that the level and lipidation state of apoE affect Ab aggregation and clearance (Bu 2009; Holtzman et al. 2012; Liao et al. 2017).”
BackgroundTargeting of nonlipidated, aggregated apoE with antibodies inhibits amyloid accumulation
Liao, F., Li, A., Xiong, M., Bien-Ly, N., Jiang, H., Zhang, Y., Finn, M. B., Hoyle, R., Keyser, J., Lefton, K. B., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci96429 · Cited by 178
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
Anti-apoE immunotherapy inhibits amyloid accumulation in a transgenic mouse model of Aβ amyloidosis
Kim, J., Eltorai, A. E. M., Jiang, H., Liao, F., Verghese, P. B., Kim, J., Stewart, F. R., Basak, J. M., & Holtzman, D. M. (2012) · Journal of Experimental Medicine · doi:10.1084/jem.20121274 · Cited by 160 · cited 2×
“Furthermore, immunotherapy against apoEwas associatedwith reducedAb deposition inAD mice (Kim et al. 2012), an effect that has recently been recapitulated using an antibody targeting only non-lipidated forms of apoE (Liao et al. 2018).”
BackgroundFitz, N. F., Cronican, A. A., Lefterov, I., & Koldamova, R. (2013) · Science · doi:10.1126/science.1235809 · Cited by 151
ATP-binding cassette transporter A1: From metabolism to neurodegeneration
Koldamova, R., Fitz, N. F., & Lefterov, I. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.05.007 · Cited by 144 · cited 1×
“As the lipidation status of apoE affects its function and receptorbinding capacity (Bu 2009; Koldamova et al. 2014), deficits in lipidation may underlie the pathogenic effects of apoE4.”
BackgroundVeeraraghavalu, K., Zhang, C., Miller, S., Hefendehl, J. K., Rajapaksha, T. W., Ulrich, J., Jucker, M., Holtzman, D. M., Tanzi, R. E., Vassar, R., et al. (2013) · Science · doi:10.1126/science.1235505 · Cited by 133
Tesseur, I., Lo, A. C., Roberfroid, A., Dietvorst, S., Van Broeck, B., Borgers, M., Gijsen, H., Moechars, D., Mercken, M., Kemp, J., et al. (2013) · Science · doi:10.1126/science.1233937 · Cited by 128
Apolipoprotein E Receptors Mediate the Effects of β-Amyloid on Astrocyte Cultures
LaDu, M. J., Shah, J. A., Reardon, C. A., Getz, G. S., Bu, G., Hu, J., Guo, L., & Van Eldik, L. J. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m000602200 · Cited by 103
Nuclear receptors in neurodegenerative diseases
Skerrett, R., Malm, T., & Landreth, G. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.05.019 · Cited by 94
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
Apolipoprotein E Genotype Affects Size of ApoE Complexes in Cerebrospinal Fluid
Heinsinger, N. M., Gachechiladze, M. A., & Rebeck, G. W. (2016) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlw067 · Cited by 74
Self-citation
Flagged first, then by citations
Research works printed but not linked: 60
- 10.1194/jlr.P800003-JLR200 · DOI
- 10.1523/JNEUROSCI.5198-13.2014 · DOI · Paper page
- 10.3233/JAD-160467 · DOI · Paper page
- 10.1194/jlr.M600214-JLR200 · DOI
- 10.1073/pnas.1106420108 · DOI · Paper page
- 10.1126/science.8346443 · DOI · Paper page
- 10.1007/s11481-015-9627-8 · DOI
- 10.1093/hmg/dds296 · DOI · Paper page
- 10.1074/jbc.M110.108100 · DOI · Paper page
- 10.1111/cts.12487 · DOI
- 10.1194/jlr.M014365 · DOI · Paper page
- 10.3233/JAD-161056 · DOI
- 10.1186/s13024-016-0099-y · DOI · Paper page
- 10.1097/MED.0000000000000045 · DOI
- 10.1038/nrm2101 · DOI · Paper page
- 10.1016/j.nbd.2009.03.007 · DOI
- 10.3233/JAD-122377 · DOI
- 10.1001/jamaneurol.2013.396 · DOI
- 10.1126/science.1072994 · DOI · Paper page
- 10.1038/nrd4280 · DOI · Paper page
- 10.1016/j.nbd.2014.07.015 · DOI
- 10.1016/j.nbd.2014.08.025 · DOI · Paper page
- 10.1016/j.neuroscience.2006.06.056 · DOI
- 10.1111/j.1749-6632.2000.tb06919.x · DOI · Paper page
- 10.1083/jcb.116.5.1071 · DOI
- 10.1074/jbc.M110.127738 · DOI
- 10.1021/jm4005847 · DOI
- 10.1093/brain/awt062 · DOI
- 10.1074/jbc.M110.127829 · DOI
- 10.1097/FJC.0b013e3181edaf69 · DOI
- 10.1016/j.nbd.2004.11.005 · DOI · Paper page
- 10.1101/cshperspect.a006338 · DOI · Paper page
- 10.1161/01.ATV.0000165694.39518.95 · DOI
- 10.2174/138945008783755584 · DOI
- 10.1021/mp200530q · DOI
- 10.1152/physrev.00005.2005 · DOI
- 10.1016/j.pharmthera.2010.12.003 · DOI
- 10.1074/jbc.274.39.27925 · DOI
- 10.1016/j.bbadis.2015.10.005 · DOI
- 10.1016/j.brainres.2012.01.017 · DOI
- 10.1073/pnas.95.26.15598 · DOI
- 10.1212/WNL.43.8.1467 · DOI · Paper page
- Segrest J. P., 1983, Studies of synthetic peptide analogs of the amphipathic helix. Competitive displacement of exchangeable apolipoproteins from native lipoproteins, J. Biol. Chem., 258, 2290, 10.1016/S0021-9258(18)32921-1 · DOI
- 10.1016/S0022-2275(20)41536-6 · DOI
- 10.15252/emmm.201606210 · DOI · Paper page
- 10.1021/nn4058215 · DOI · Paper page
- 10.1073/pnas.90.5.1977 · DOI · Paper page
- 10.1074/jbc.M114.600833 · DOI · Paper page
- 10.1186/1750-1326-9-2 · DOI · Paper page
- 10.1194/jlr.M500240-JLR200 · DOI
- 10.2147/NDT.S61309 · DOI · Paper page
- 10.1073/pnas.1220484110 · DOI · Paper page
- 10.1074/jbc.M508780200 · DOI · Paper page
- 10.1194/jlr.M011098 · DOI
- 10.1016/S0021-9258(19)52510-8 · DOI · Paper page
- 10.1194/jlr.R051367 · DOI
- 10.1006/bbrc.1993.1423 · DOI · Paper page
- 10.1620/tjem.220.223 · DOI
- 10.1523/JNEUROSCI.5476-05.2006 · DOI · Paper page
- 10.1073/pnas.0701096104 · DOI · Paper page
Cited by
Sorted by citations
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
ApoE4 Alters ABCA1 Membrane Trafficking in Astrocytes
Rawat, V., Wang, S., Sima, J., Bar, R., Liraz, O., Gundimeda, U., Parekh, T., Chan, J., Johansson, J. O., Tang, C., et al. (2019) · The Journal of Neuroscience · doi:10.1523/jneurosci.1400-19.2019 · Cited by 165
Isoform- and cell-state-specific lipidation of ApoE in astrocytes
Lindner, K., Beckenbauer, K., van Ek, L. C., Titeca, K., de Leeuw, S. M., Awwad, K., Hanke, F., Korepanova, A. V., Rybin, V., van der Kam, E. L., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110435 · Cited by 84
Metadata
- Authors
- Chernick, D., Ortiz‐Valle, S., Jeong, A., Swaminathan, S. K., Kandimalla, K. K., Rebeck, G. W., & Li, L.
- Affiliations
- Department of Pharmacology University of Minnesota Minneapolis Minnesota USA
- Department of Experimental and Clinical Pharmacology University of Minnesota Minneapolis Minnesota USA
- Department of Pharmaceutics University of Minnesota Minneapolis Minnesota USA
- Department of Neuroscience Georgetown University Washington District of Columbia USA
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2018-11-26
- Volume
- 147
- Issue
- 5
- Pages
- 647-662
- ISSN
- 0022-3042
- 1471-4159
- PMC
- PMC6314045
- Cited by
- 51
- References
- 32
- Language
- en
- Funders
- National Institute on Aging (AG056025, AG056976, AG058081)
- National Institute of Neurological Disorders and Stroke (NS100704)
- National Institute on Drug Abuse (T32DA007097)
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