Human cerebrospinal fluid contains diverse lipoprotein subspecies enriched in proteins implicated in central nervous system health
Open accessAbstract
Lipoproteins in cerebrospinal fluid (CSF) of the central nervous system (CNS) resemble plasma high-density lipoproteins (HDLs), which are a compositionally and structurally diverse spectrum of nanoparticles with pleiotropic functionality. Whether CSF lipoproteins (CSF-Lps) exhibit similar heterogeneity is poorly understood because they are present at 100-fold lower concentrations than plasma HDL. To investigate the diversity of CSF-Lps, we developed a sensitive fluorescent technology to characterize lipoprotein subspecies in small volumes of human CSF. We identified 10 distinctly sized populations of CSF-Lps, most of which were larger than plasma HDL. Mass spectrometric analysis identified 303 proteins across the populations, over half of which have not been reported in plasma HDL. Computational analysis revealed that CSF-Lps are enriched in proteins important for wound healing, inflammation, immune response, and both neuron generation and development. Network analysis indicated that different subpopulations of CSF-Lps contain unique combinations of these proteins. Our study demonstrates that CSF-Lp subspecies likely exist that contain compositional signatures related to CNS health.
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The CNS primarily contains HDL-like particles, many of which harbor ApoE and can engage LDLR.
“the CNS primarily contains HDL-like particles, many of which harbors ApoE and can thus engage LDLR56.”
From Decreased lipidated ApoE‐receptor interactions confer protection against pathogenicity of ApoE and its lipid cargoes in lysosomes (2025) · cites this paper as [56]
The Introduction describes CSF lipoproteins as HDL-like and says APOE is their primary scaffold protein; the Discussion reports that APOE co-elutes with the bulk of CSF lipid. But the paper does not say these particles engage LDLR, and its Results place the bulk of CSF lipoprotein lipid between the plasma VLDL/LDL and large-HDL size ranges, rather than establishing that the CNS primarily contains HDL-sized particles. Page numbers were not available in our copy. (LLM, conf=0.85)
Experimental — accuracy not yet measuredApoE is associated with virtually all plasma LNPs, albeit in varying amounts.
“ApoE is associated with virtually all plasma LNPs, albeit in varying amounts.5”
From ApoE is Secreted as a Lipid Nanoparticle by Mammalian Cells: Implications for Alzheimer’s Disease Pathogenesis (2025) · cites this paper as [5]
The Discussion (page unavailable) reports APOE across multiple cerebrospinal-fluid lipoprotein populations of various sizes. That supports a broad association in CSF, but not the claim that APOE is associated with virtually all plasma lipoprotein particles in varying amounts. (LLM, conf=0.86)
Experimental — accuracy not yet measured
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Szklarczyk, D., Gable, A. L., Nastou, K. C., Lyon, D., Kirsch, R., Pyysalo, S., Doncheva, N. T., Legeay, M., Fang, T., Bork, P., et al. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkaa1074 · Cited by 8,056 · see citing works
Sherman, B. T., Hao, M., Qiu, J., Jiao, X., Baseler, M., Lane, H. C., Imamichi, T., & Chang, W. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac194 · Cited by 6,152 · see citing works
The MaxQuant computational platform for mass spectrometry-based shotgun proteomics
Tyanova, S., Temu, T., & Cox, J. (2016) · Nature Protocols · doi:10.1038/nprot.2016.136 · Cited by 4,691 · see citing works
Complement and its role in innate and adaptive immune responses
Dunkelberger, J. R., & Song, W.-C. (2010) · Cell Research · doi:10.1038/cr.2009.139 · Cited by 1,932 · see citing works
Lipid-associated macrophages control metabolic homeostasis in a Trem2-dependent manner
Jaitin, D. A., Adlung, L., Thaiss, C. A., Weiner, A., Li, B., Descamps, H., Lundgren, P., Bleriot, C., Liu, Z., Deczkowska, A., et al. (2019) · Cell · doi:10.1016/j.cell.2019.05.054 · Cited by 1,377 · see citing works
Vaisar, T., Pennathur, S., Green, P. S., Gharib, S. A., Hoofnagle, A. N., Cheung, M. C., Byun, J., Vuletic, S., Kassim, S., Singh, P., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci26206 · Cited by 942 · see citing works
Self-citationFibrin structure and wound healing
LAURENS, N., KOOLWIJK, P., & DE MAAT, M. P. M. (2006) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2006.01861.x · Cited by 724 · see citing works
Pitas, R. E., Boyles, J. K., Lee, S. H., Hui, D., & Weisgraber, K. H. (1987) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)47945-8 · Cited by 714 · see citing works
Navab, M., Hama, S. Y., Anantharamaiah, G. M., Hassan, K., Hough, G. P., Watson, A. D., Reddy, S. T., Sevanian, A., Fonarow, G. C., & Fogelman, A. M. (2000) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)33462-3 · Cited by 663 · see citing works
Characterization of human high-density lipoproteins by gradient gel electrophoresis
Blanche, P. J., Gong, E. L., Forte, T. M., & Nichols, A. V. (1981) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(81)90253-8 · Cited by 614 · 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
Elshourbagy, N. A., Liao, W. S. ‐., Mahley, R. W., & Taylor, J. M. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.1.203 · Cited by 509 · see citing works
Langmann, T., Klucken, J., Reil, M., Liebisch, G., Luciani, M., Chimini, G., Kaminski, W. E., & Schmitz, G. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.0406 · Cited by 492 · see citing works
Albumin as Fatty Acid Transporter
Vusse, G. J. (2009) · Drug Metabolism and Pharmacokinetics · doi:10.2133/dmpk.24.300 · Cited by 482 · see citing works
High density lipoproteins and coronary heart disease
Barter, P. J., & Rye, K.-A. (1996) · Atherosclerosis · doi:10.1016/0021-9150(95)05675-0 · Cited by 377 · see citing works
Phenotypes of apolipoprotein B and apolipoprotein E after liver transplantation.
Linton, M. F., Gish, R., Hubl, S. T., Bütler, E., Esquivel, C., Bry, W. I., Boyles, J. K., Wardell, M. R., & Young, S. G. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115288 · Cited by 367 · see citing works
ApoE attenuates unresolvable inflammation by complex formation with activated C1q
Yin, C., Ackermann, S., Ma, Z., Mohanta, S. K., Zhang, C., Li, Y., Nietzsche, S., Westermann, M., Peng, L., Hu, D., et al. (2019) · Nature Medicine · doi:10.1038/s41591-018-0336-8 · Cited by 305 · see citing works
Characterization of four lipoprotein classes in human cerebrospinal fluid
Koch, S., Donarski, N., Goetze, K., Kreckel, M., Stuerenburg, H.-J., Buhmann, C., & Beisiegel, U. (2001) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)31605-9 · Cited by 298 · see citing works
De Schepper, S., Ge, J. Z., Sierksma, A., Crowley, G., Ferreira, L. S. S., Garceau, D., Toomey, C. E., Sokolova, D., Rueda-Carrasco, J., Shin, S.-H., et al. (2023) · Nature Neuroscience · doi:10.1038/s41593-023-01257-z · Cited by 295 · see citing works
Nascent astrocyte particles differ from lipoproteins in CSF
LaDu, M. J., Gilligan, S. M., Lukens, J. R., Cabana, V. G., Reardon, C. A., Van Eldik, L. J., & Holtzman, D. M. (1998) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1998.70052070.x · Cited by 285 · cited 13× · see citing works
“Unexpectedly, we also observed particles in the size range of VLDL/LDL that, like plasma VLDL/LDL, were enriched in fibrinogens and alpha-2-macroglobulin (A2MG) (2).”
BackgroundMethodResultInfluentialEffects of High-Density Lipoproteins on Pancreatic β-Cell Insulin Secretion
Fryirs, M. A., Barter, P. J., Appavoo, M., Tuch, B. E., Tabet, F., Heather, A. K., & Rye, K. (2010) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.110.207373 · Cited by 283 · see citing works
Apolipoproteins in human cerebrospinal fluid.
Roheim, P. S., Carey, M., Forte, T., & Vega, G. L. (1979) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.76.9.4646 · Cited by 282 · see citing works
Microglial translational profiling reveals a convergent APOE pathway from aging, amyloid, and tau
Kang, S. S., Ebbert, M. T. W., Baker, K. E., Cook, C., Wang, X., Sens, J. P., Kocher, J.-P., Petrucelli, L., & Fryer, J. D. (2018) · Journal of Experimental Medicine · doi:10.1084/jem.20180653 · Cited by 260 · see citing works
HDL and cholesterol handling in the brain
Vitali, C., Wellington, C. L., & Calabresi, L. (2014) · Cardiovascular Research · doi:10.1093/cvr/cvu148 · Cited by 254 · see citing works
Apolipoprotein A-I structural organization in high-density lipoproteins isolated from human plasma
Huang, R., Silva, R. A. G. D., Jerome, W. G., Kontush, A., Chapman, M. J., Curtiss, L. K., Hodges, T. J., & Davidson, W. S. (2011) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2028 · Cited by 246 · see citing works
Self-citationGordon, S. M., Deng, J., Lu, L. J., & Davidson, W. S. (2010) · Journal of Proteome Research · doi:10.1021/pr100520x · Cited by 243 · see citing works
Self-citationWhat are lipoproteins doing in the brain?
Wang, H., & Eckel, R. H. (2014) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2013.10.003 · Cited by 234 · see citing works
Role of Lipoproteins in the Delivery of Lipids to Axons during Axonal Regeneration
de Chaves, E. I. P., Rusiñol, A. E., Vance, D. E., Campenot, R. B., & Vance, J. E. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.49.30766 · Cited by 209 · see citing works
Structure of apolipoprotein A-I in spherical high density lipoproteins of different sizes
Silva, R. A. G. D., Huang, R., Morris, J. C., Fang, J., Gracheva, E. O., Ren, G., Kontush, A., Jerome, W. G., Rye, K., & Davidson, W. S. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0803626105 · Cited by 206 · see citing works
Self-citationApolipoproteins in the brain: implications for neurological and psychiatric disorders
Elliott, D. A., Weickert, C. S., & Garner, B. (2010) · Clinical Lipidology · doi:10.2217/clp.10.37 · Cited by 196 · see citing works
HDL and cognition in neurodegenerative disorders
Hottman, D. A., Chernick, D., Cheng, S., Wang, Z., & Li, L. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.07.015 · Cited by 184 · see citing works
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 · see citing works
Demeester, N., Castro, G., Desrumaux, C. M., Geitere, C. D., Fruchart, J., Santens, P., Mulleners, E., Engelborghs, S., Deyn, P. P. D., Vandekerckhove, J. S., et al. (2000) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)32039-3 · Cited by 157 · see citing works
Levi, O., Jongen‐Rêlo, A. L., Feldon, J., Roses, A. D., & Michaelson, D. M. (2003) · Neurobiology of Disease · doi:10.1016/s0969-9961(03)00045-7 · Cited by 145 · see citing works
Structural basis of transfer between lipoproteins by cholesteryl ester transfer protein
Zhang, L., Feng, Y., Zhang, S., Lei, D., Charles, M. A., Cavigiolio, G., Oda, M. N., Krauss, R. M., Weisgraber, K. H., Rye, K.-A., et al. (2012) · Nature Chemical Biology · doi:10.1038/nchembio.796 · Cited by 141 · see citing works
The HDL Proteome Watch: Compilation of studies leads to new insights on HDL function
Davidson, W. S., SHAH, A. S., Sexmith, H., & Gordon, S. M. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2021.159072 · Cited by 138 · see citing works
Self-citationAoto, J. N., Földy, C., Ciurea-Ilcus, S., Tabuchi, K., & Südhof, T. C. (2015) · Nature Neuroscience · doi:10.1038/nn.4037 · Cited by 134 · see citing works
Koudinov, A. R., Koudinova, N. V., Kumar, A. R., Beavis, R. C., & Ghiso, J. A. (1996) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.0940 · Cited by 129 · see citing works
Navab, M., Hama, S. Y., Cooke, C. J., Anantharamaiah, G. M., Chaddha, M., Jin, L., Subbanagounder, G., Faull, K. F., Reddy, S. T., Miller, N. E., et al. (2000) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)33461-1 · Cited by 126 · see citing works
Osterhout, J. A., Stafford, B. K., Nguyen, P. L., Yoshihara, Y., & Huberman, A. D. (2015) · Neuron · doi:10.1016/j.neuron.2015.04.005 · Cited by 104 · see citing works
A thumbwheel mechanism for APOA1 activation of LCAT activity in HDL[S]
Cooke, A. L., Morris, J. C., Melchior, J., Street, S. E., Jerome, W. G., Huang, R., Herr, A. B., Smith, L. E., Segrest, J. P., Remaley, A. T., et al. (2018) · Journal of Lipid Research · doi:10.1194/jlr.m085332 · Cited by 93 · see citing works
Self-citationNeural Cell Adhesion Molecule NrCAM Regulates Semaphorin 3F-Induced Dendritic Spine Remodeling
Demyanenko, G. P., Mohan, V., Zhang, X., Brennaman, L. H., Dharbal, K. E. S., Tran, T. S., Manis, P. B., & Maness, P. F. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.1774-14.2014 · Cited by 92 · see citing works
Molina‐Portela, M. D. P., Samanovic, M. I., & Raper, J. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20071463 · Cited by 89 · see citing works
The Effects of Type 2 Diabetes on Lipoprotein Composition and Arterial Stiffness in Male Youth
Gordon, S. M., Davidson, W. S., Urbina, E. M., Dolan, L. M., Heink, A., Zang, H., Lu, L. J., & SHAH, A. S. (2013) · Diabetes · doi:10.2337/db12-1753 · Cited by 83 · see citing works
Self-citationDislich, B., Wohlrab, F., Bachhuber, T., Müller, S. A., Kuhn, P., Hogl, S., Meyer‐Luehmann, M., & Lichtenthaler, S. F. (2015) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m114.041533 · Cited by 82 · see citing works
Schilling, S., Mehr, A., Ludewig, S., Stephan, J., Zimmermann, M., August, A., Strecker, P., Körte, M., Koo, E. H., Müller, U., et al. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.1875-16.2017 · Cited by 77 · see citing works
Gordon, S. M., Deng, J., Tomann, A. B., SHAH, A. S., Lu, L. J., & Davidson, W. S. (2013) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m113.028134 · Cited by 72 · see citing works
Self-citationMelchior, J., Street, S. E., Andraski, A. B., Furtado, J. D., Sacks, F. M., Shute, R. L., Greve, E. I., Swertfeger, D. K., Li, H., SHAH, A. S., et al. (2017) · Journal of Lipid Research · doi:10.1194/jlr.m075382 · Cited by 72 · see citing works
Self-citationApolipoprotein B is a novel marker for early tau pathology in Alzheimer's disease
Picard, C., Nilsson, N., Labonté, A., Auld, D., Rosa‐Neto, P., Initiative, T. A. D. N., Ashton, N. J., Zetterberg, H., Blennow, K., Breitner, J. C. B., et al. (2022) · Alzheimer's & Dementia · doi:10.1002/alz.12442 · Cited by 66 · see citing works
A rapid and accurate approach for prediction of interactomes from co-elution data (PrInCE)
Stacey, R. G., Skinnider, M. A., Scott, N. E., & Foster, L. J. (2017) · BMC Bioinformatics · doi:10.1186/s12859-017-1865-8 · Cited by 65 · see citing works
Sacks, F. M., Liang, L., Furtado, J. D., Cai, T., Davidson, W. S., He, Z., McClelland, R. L., Rimm, E. B., & Jensen, M. K. (2020) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.120.314609 · Cited by 57 · see citing works
Self-citationBlood Contamination in CSF and Its Impact on Quantitative Analysis of Alpha-Synuclein
Barkovits, K., Kruse, N., Linden, A., Tönges, L., Pfeiffer, K., Mollenhauer, B., & Marcus, K. (2020) · Cells · doi:10.3390/cells9020370 · Cited by 54 · see citing works
Plxdc2 Is a Mitogen for Neural Progenitors
Miller-Delaney, S. F. C., Lieberam, I., Murphy, P., & Mitchell, K. J. (2011) · PLoS ONE · doi:10.1371/journal.pone.0014565 · Cited by 53 · see citing works
High density lipoproteins selectively promote the survival of human regulatory T cells
Rueda, C. M., Rodríguez-Perea, A. L., Moreno‐Fernandez, M. E., Jackson, C. M., Melchior, J., Davidson, W. S., & Chougnet, C. A. (2017) · Journal of Lipid Research · doi:10.1194/jlr.m072835 · Cited by 52 · see citing works
Self-citationGuyton, J. R., Miller, S., Martin, M. E., Khan, W. A., Roses, A. D., & Strittmatter, W. J. (1998) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1998.70031235.x · Cited by 47 · see citing works
Weight loss surgery in adolescents corrects high-density lipoprotein subspecies and their function
Davidson, W. S., Inge, T. H., Sexmith, H., Heink, A., Elder, D. A., Hui, D. Y., Melchior, J., Kelesidis, T., & Shah, A. S. (2016) · International Journal of Obesity · doi:10.1038/ijo.2016.190 · Cited by 43 · see citing works
Self-citationThe pleiotropic vasoprotective functions of high density lipoproteins (HDL)
Boyce, G. K., Button, E. B., Sonja, S. V., & Wellington, C. L. (2017) · Journal of Biomedical Research · doi:10.7555/jbr.31.20160103 · Cited by 41 · see citing works
Davidson, W. S., Cooke, A. L., Swertfeger, D. K., & SHAH, A. S. (2021) · Current Atherosclerosis Reports · doi:10.1007/s11883-021-00925-4 · Cited by 41 · see citing works
Self-citationDickkopf‐related protein 3 is a potential Aβ‐associated protein in Alzheimer's Disease
Bruggink, K. A., Kuiperij, H. B., Gloerich, J., Otte‐Höller, I., Rozemüller, A. J. M., Claassen, J. A. H. R., Küsters, B., & Verbeek, M. M. (2015) · Journal of Neurochemistry · doi:10.1111/jnc.13216 · Cited by 35 · see citing works
Ashraf, A., Ashton, N. J., Chatterjee, P., Goozee, K. G., Shen, K., Fripp, J., Ames, D. J., Rowe, C. C., Masters, C. L., Villemagne, V. L., et al. (2020) · Alzheimer s Research & Therapy · doi:10.1186/s13195-020-00634-1 · Cited by 31 · see citing works
Apolipoprotein A-I modulates HDL particle size in the absence of apolipoprotein A-II
Melchior, J., Street, S. E., Vaisar, T., Hart, R. C., Jerome, W. G., Kuklenyik, Z., Clouet-Foraison, N., Thornock, C., Bedi, S., SHAH, A. S., et al. (2021) · Journal of Lipid Research · doi:10.1016/j.jlr.2021.100099 · Cited by 31 · see citing works
Self-citationResolution of Lipoprotein Subclasses by Charge Detection Mass Spectrometry
Lutomski, C. A., Gordon, S. M., Remaley, A. T., & Jarrold, M. F. (2018) · Analytical Chemistry · doi:10.1021/acs.analchem.8b01127 · Cited by 31 · see citing works
Developmental role of the cell adhesion molecule Contactin-6 in the cerebral cortex and hippocampus
Zuko, A., Oguro‐Ando, A., van Dijk, R. E., Gregorio-Jordan, S., van der Zwaag, B., & Burbach, J. P. H. (2016) · Cell Adhesion & Migration · doi:10.1080/19336918.2016.1155018 · Cited by 30 · see citing works
Davidson, W. S., Heink, A., Sexmith, H., Dolan, L. M., Gordon, S. M., Otvos, J. D., Melchior, J., Elder, D. A., Khoury, J. C., Geh, E. N., et al. (2017) · Journal of Lipid Research · doi:10.1194/jlr.m078667 · Cited by 30 · see citing works
Self-citationProteomic Substrate Identification for Membrane Proteases in the Brain
Müller, S. A., Scilabra, S. D., & Lichtenthaler, S. F. (2016) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2016.00096 · Cited by 29 · see citing works
Melchior, J., Swertfeger, D. K., Morris, J. C., Street, S. E., Warshak, C. R., Welge, J. A., Remaley, A. T., Catov, J. M., Davidson, W. S., & Woollett, L. A. (2021) · Journal of Lipid Research · doi:10.1016/j.jlr.2021.100107 · Cited by 25 · see citing works
Self-citationCleland, N. R. W., & Bruce, K. D. (2022) · Biochimie · doi:10.1016/j.biochi.2022.08.012 · Cited by 23 · see citing works
Self-citationFaizullin, D. A., Valiullina, Y. A., Salnikov, V. V., & Zuev, Y. F. (2019) · Nanomedicine Nanotechnology Biology and Medicine · doi:10.1016/j.nano.2019.102098 · Cited by 21 · see citing works
Gibson, C. M., Kazmi, S. H. A., Korjian, S., Chi, G., Phillips, A. T., Montazerin, S. M., Duffy, D., Zheng, B., Heise, M. A., Liss, C. L., et al. (2022) · Journal of Cardiovascular Pharmacology and Therapeutics · doi:10.1177/10742484221121507 · Cited by 20 · see citing works
Li, H., Gordon, S. M., Zhu, X., Deng, J., Swertfeger, D. K., Davidson, W. S., & Lu, L. J. (2015) · Journal of Proteome Research · doi:10.1021/acs.jproteome.5b00419 · Cited by 19 · see citing works
Self-citationApolipoprotein B-100-mediated motor neuron degeneration in sporadic amyotrophic lateral sclerosis
Wong, J. K., Roselle, A. K., Shue, T. M., Shimshak, S. J. E., Beaty, J. M., Celestin, N., Gao, I., Griffin, R., Cudkowicz, M., & Sadiq, S. A. (2022) · Brain Communications · doi:10.1093/braincomms/fcac207 · Cited by 16 · see citing works
Taylor, H. A., Simmons, K. J., Clavane, E. M., Trevelyan, C. J., Brown, J., Przemyłska, L., Watt, N. T., Matthews, L. C., & Meakin, P. J. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23094568 · Cited by 13 · see citing works
Didichenko, S. A., Navdaev, A., Saxenhofer, M., Graeter, S., Schaub, A., Rovó, A., Kato, G. J., & Kingwell, B. A. (2022) · Blood · doi:10.1182/blood-2022-158405 · Cited by 1 · see citing works
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Guo, J. L., Braun, D., Fitzgerald, G. A., Hsieh, Y.-T., Rougé, L., Litvinchuk, A., Steffek, M., Propson, N. E., Heffner, C. M., Discenza, C., et al. (2025) · Cell · doi:10.1016/j.cell.2024.10.027 · Cited by 91 · see citing works
“53 While LDL biology is mostly relevant for peripheral diseases, 32,54,55 the CNS primarily contains HDL-like particles, many of which harbor ApoE and can thus engage LDLR. 56 LDLR’s ligands in the CNS, besides ApoE, are not well defined.”
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Sprenger, K. G., Lietzke, E. E., Melchior, J., & Bruce, K. D. (2025) · Journal of Lipid Research · doi:10.1016/j.jlr.2025.100872 · Cited by 40 · see citing works
Self-citationTobeh, N. S., & Bruce, K. D. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1259012 · Cited by 31 · see citing works
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Tsujita, M., Melchior, J., & Yokoyama, S. (2024) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.123.318284 · Cited by 21 · see citing works
Self-citationЛю, Ч., Liu, J., Wang, Y., Xu, S.-F., & Yu, L.-M. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-05629-3 · Cited by 21 · see citing works
Yue, C., Fu, Y., Zhao, Y., Ou, Y., Sun, Y., & Tan, L. (2024) · Brain Network Disorders · doi:10.1016/j.bnd.2024.10.006 · Cited by 15 · see citing works
Zhu, P., Xiao, L., & Wang, Y. (2025) · Fluids and Barriers of the CNS · doi:10.1186/s12987-025-00721-1 · Cited by 15 · see citing works
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Lietzke, E. E., Saeb, D., Aldrich, E. C., Bruce, K. D., & Sprenger, K. G. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70120 · Cited by 14 · see citing works
Self-citationBorràs, C., Canyelles, M., Santos, D., Rotllán, N., Núñez, E., Vázquez, J., Maspoch, D., Cano‐Sarabia, M., Zhao, Q., Carmona‐Iragui, M., et al. (2025) · Journal of Lipid Research · doi:10.1016/j.jlr.2025.100865 · Cited by 12 · see citing works
von Eckardstein, A., & Robert, J. (2025) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.125.321546 · Cited by 8 · see citing works
Strickland, M. R., Wang, Z., Golden, L. R., Wang, H., Lu, P., Ren, Y., Tabor, G. T., Zhao, N., Ulrich, J. D., Han, X., et al. (2026) · Journal of Lipid Research · doi:10.1016/j.jlr.2026.101000 · Cited by 8 · see citing works
APOE3 astrocytes can rescue lipid abnormalities and dystrophic neurites of APOE4 human neurons
Halim, D. O., Biase, E. D., Rajon, A., Jordi, L., Hallett, P. J., & Ole Isacson, A. (2026) · PNAS Nexus · doi:10.1093/pnasnexus/pgag053 · Cited by 6 · see citing works
Nowacka, A., Śniegocki, M., & Ziółkowska, E. (2025) · Cells · doi:10.3390/cells14181479 · Cited by 5 · see citing works
Yanagidaira, M., Nagata, T., Hasegawa, J., Ishii, T., Ebihara, S., Nawa, M., & Yokota, T. (2025) · Nature Communications · doi:10.1038/s41467-025-66765-x · Cited by 3 · see citing works
Vaisar, T., & Ronsein, G. E. (2025) · Expert Review of Proteomics · doi:10.1080/14789450.2025.2534397 · Cited by 3 · see citing works
Self-citationHernandez Arriaza, R., Reil, D., Fatuzzo, N., Fu, M., Dai, Y., Fernandez Martinez, D., Jiang, H., Holtzman, D. M., Greicius, M. D., & Khosla, C. (2025) · Biochemistry · doi:10.1021/acs.biochem.5c00503 · Cited by 2 · see citing works
Plasmalogen deficiency and the Alzheimer’s disease risk of apolipoprotein E4
Hällqvist, J., Taanman, J., Göteson, A., Heywood, W., Schott, J. M., Hardy, J., Landén, M., Zetterberg, H., Mills, K. A., & Ginsberg, L. (2026) · Brain Communications · doi:10.1093/braincomms/fcag040 · Cited by 1 · see citing works
Zhu, B., Shao, Q., Cui, J., Zhenyan, F., & Ma, Y. (2026) · Frontiers in Medicine · doi:10.3389/fmed.2026.1765715 · Cited by 1 · see citing works
Soloey-Nilsen, H., Nygaard-Odeh, K., Kristiansen, M. G., Kvig, E. I., Brekke, O., Mollnes, T. E., Berk, M., & Reitan, S. K. (2025) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2025.1634920 · Cited by 1 · see citing works
Borràs, C., Canyelles, M., Santos, D., Rotllán, N., Núñez, E., Vázquez, J., Maspoch, D., Cano‐Sarabia, M., Carmona‐Iragui, M., Sirisi, S., et al. (2024) · Research Square · doi:10.21203/rs.3.rs-5682870/v1
Kakava, S., Melo, M. G., Cheng, W. H., Gaudio, I. D., Viertl, D., Bernhard, S., Schlumpf, E., Croyal, M., Volovičeva, E., Fan, J., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.05.23.655828
Yoshida, T., Yang, Z.-H., Ashida, S., Yu, Z., Shrivastav, S., Rojulpote, K. V., Bahar, P., Nguyen, D., Springer, D., Munasinghe, J., et al. (2025) · Clinical Science · doi:10.1042/cs20255324
From cellular cognition to psychopathology: a three-level framework of biological decision-making
Guerrero, G. L. N. (2026) · Medical Hypotheses · doi:10.1016/j.mehy.2026.111914
Verran, E., Moizan, L., Tocquer, L., Quan, F. B., & Wyart, C. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.04.14.718607
Verran, E., Moizan, L., Tocquer, L., Quan, F. B., & Wyart, C. (2026) · eLife · doi:10.7554/elife.111150
Verran, E., Moizan, L., Tocquer, L., Quan, F. B., & Wyart, C. (2026) · eLife · doi:10.7554/elife.111150.1
ApoE lipidation state directs immunometabolic reprogramming of human microglia
Shiferaw, T. G., Sarkar, S., Baker, K. M., Wooldridge, R. S., Binfet, H. M., Prozapas, V. N., Ogbu, C. P., Schepmoes, A. A., Attah, I. K., Niemeyer, C. S., et al. (2026) · Alzheimer s & Dementia · doi:10.1002/alz.71882 · Cited by 1 · see citing works
Self-citation
- Authors
- Merrill, N. J., Davidson, W. S., He, Y., Díaz Ludovico, I., Sarkar, S., Berger, M. R., McDermott, J. E., Van Eldik, L. J., Wilcock, D. M., Monroe, M. E., Kyle, J. E., Bruce, K. D., Heinecke, J. W., Vaisar, T., Raber, J., Quinn, J. F., & Melchior, J. T.
- Affiliations
- Pacific Northwest National Laboratory (US)
- University of Cincinnati (US)
- University of Washington (US)
- Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.
- Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40504, USA.
- University of Kentucky (US)
- University of Colorado Anschutz (US)
- Department of Medicine, University of Washington School of Medicine, Seattle, WA 98109, USA.
- Oregon Health & Science University (US)
- Corresponding author
- Melchior, John T.
- ORCID
- Venue
- Science Advances
- Published
- 2023-09
- Volume
- 9
- Issue
- 35
- Pages
- eadi5571-eadi5571
- ISSN
- 2375-2548 (ISSN-L)
- PMC
- PMC10468133
- OpenAlex
- W4386276912
- Cited by
- 27
- References
- 73
- Citations by year
- 2026: 9 · 2025: 13 · 2024: 4 · 2023: 1
- FWCI
- 7.23
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Science Advances (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion, cc-by)
- Funders
- National Institutes of Health
- National Institute on Aging (R03AG070480, P30AG066518, R01AG079217, P30AG072946)
- National Heart, Lung, and Blood Institute (P01HL128203)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Keywords
- high-density lipoprotein, wound healing, inflammation, immune response, neuronal development, protein network analysis
- MeSH terms
- Central Nervous System, Coloring Agents, Humans, Lipopolysaccharides, Lipoproteins, Lipoproteins, HDL
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