Apolipoproteins and their subspecies in human cerebrospinal fluid and plasma
Open accessAbstract
Introduction: Subspecies of apolipoproteins can be defined by fractionating apolipoproteins based on the presence and absence of coexisting apolipoproteins. Methods: We determined age‐ and sex‐adjusted correlations of enzyme‐linked immunosorbent assay–measured plasma and cerebrospinal fluid (CSF) apolipoproteins (apoA‐I, apoC‐III, apoE, and apoJ) or apolipoprotein subspecies (apoA‐I with and without apoC‐III, ApoE, or apoJ; apoE with and without apoC‐III or apoJ) in 22 dementia‐free participants. Results: CSF apoE did not correlate with plasma apolipoproteins or their subspecies. CSF apoJ correlated most strongly with plasma apoA‐I without apoJ (r = 0.7). CSF apoA‐I correlated similarly strong with plasma total apoA‐I and all apoA‐I subspecies (r ≥ 0.4) except for apoA‐I with apoE (r = 0.3) or apoA‐I with apoJ (r = 0.3). CSF apoC‐III was most strongly correlated with plasma apoA‐I with apoC‐III (r = 0.7). Discussion: CSF levels of some apolipoproteins implicated in the pathophysiology of dementia might be better approximated by specific plasma apolipoprotein subspecies than total plasma concentrations.
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Human CSF ApoE concentrations are ~7-9 μg/ml (~206-265 nM).
“Human CSF ApoE concentrations were reported to be ~7–9 μg/ml (~206–265 nM)”
From Decreased lipidated ApoE‐receptor interactions confer protection against pathogenicity of ApoE and its lipid cargoes in lysosomes (2025) · cites this paper as [48]
The Results report that apoE was measured in human CSF and refer to Table 1, but the passages available from our copy give no absolute CSF apoE concentration. Searches for 7–9 μg/ml, 206–265 nM, and CSF apoE median concentrations did not retrieve the claimed values, so the numerical claim cannot be verified from our copy. (LLM, conf=0.72)
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Harold, D., Abraham, R., Hollingworth, P., Sims, R., Gerrish, A., Hamshere, M. L., Pahwa, J. S., Moskvina, V., Dowzell, K., Williams, A., et al. (2009) · Nature Genetics · doi:10.1038/ng.440 · Cited by 3,326 · see citing works
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 · 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
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Research works printed but not linked: 22
- [1]Koch M. Jensen M.K. HDL-cholesterol and apolipoproteins in relation to dementia Curr Opin Lipidol 27 2016 76 87 26709470 PMC4703432
- [3]Holtzman D.M. Role of apoe/Abeta interactions in the pathogenesis of Alzheimer's disease and cerebral amyloid angiopathy J Mol Neurosci 17 2001 147 155 11816788
- [4]Zlokovic B.V. Deane R. Sallstrom J. Chow N. Miano J.M. Neurovascular pathways and Alzheimer amyloid beta-peptide Brain Pathol 15 2005 78 83 15779240 PMC8095816
- [6]Wang X. Luebbe P. Gruenstein E. Zemlan F. Apolipoprotein E (ApoE) peptide regulates tau phosphorylation via two different signaling pathways J Neurosci Res 51 1998 658 665 9512010
- [7]Shih Y.H. Tsai K.J. Lee C.W. Shiesh S.C. Chen W.T. Pai M.C. Apolipoprotein C-III is an amyloid-beta-binding protein and an early marker for Alzheimer's disease J Alzheimers Dis 41 2014 855 865 24685634
- [8]Llano D.A. Devanarayan V. Simon A.J. Evaluation of plasma proteomic data for Alzheimer disease state classification and for the prediction of progression from mild cognitive impairment to Alzheimer disease Alzheimer Dis Assoc Disord 27 2013 233 243 23023094
- [9]Dubois B. Feldman H.H. Jacova C. Hampel H. Molinuevo J.L. Blennow K. Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria Lancet Neurol 13 2014 614 629 24849862
- [10]Olsson B. Lautner R. Andreasson U. Ohrfelt A. Portelius E. Bjerke M. CSF and blood biomarkers for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis Lancet Neurol 15 2016 673 684 27068280
- [11]Winblad B. Amouyel P. Andrieu S. Ballard C. Brayne C. Brodaty H. Defeating Alzheimer's disease and other dementias: a priority for European science and society Lancet Neurol 15 2016 455 532 26987701
- [13]Reiber H. Proteins in cerebrospinal fluid and blood: barriers, CSF flow rate and source-related dynamics Restor Neurol Neurosci 21 2003 79 96 14530572
- [14]Reiber H. Otto M. Trendelenburg C. Wormek A. Reporting cerebrospinal fluid data: knowledge base and interpretation software Clin Chem Lab Med 39 2001 324 332 11388657
- [15]Roheim P.S. Carey M. Forte T. Vega G.L. Apolipoproteins in human cerebrospinal fluid Proc Natl Acad Sci U S A 76 1979 4646 4649 291993 PMC411636
- [16]Koch S. Donarski N. Goetze K. Kreckel M. Stuerenburg H.J. Buhmann C. Characterization of four lipoprotein classes in human cerebrospinal fluid J Lipid Res 42 2001 1143 1151 11441143
- [17]Toledo J.B. Da X. Weiner M.W. Wolk D.A. Xie S.X. Arnold S.E. CSF Apo-E levels associate with cognitive decline and MRI changes Acta Neuropathol 127 2014 621 632 24385135 PMC3988233
- [18]Martinez-Morillo E. Hansson O. Atagi Y. Bu G. Minthon L. Diamandis E.P. Total apolipoprotein E levels and specific isoform composition in cerebrospinal fluid and plasma from Alzheimer's disease patients and controls Acta Neuropathol 127 2014 633 643 24633805
- [19]Liu M. Kuhel D.G. Shen L. Hui D.Y. Woods S.C. Apolipoprotein E does not cross the blood-cerebrospinal fluid barrier, as revealed by an improved technique for sampling CSF from mice Am J Physiol Regul Integr Comp Physiol 303 2012 R903 R908 22933021 PMC3517701
- [20]Shayo M. McLay R.N. Kastin A.J. Banks W.A. The putative blood-brain barrier transporter for the beta-amyloid binding protein apolipoprotein j is saturated at physiological concentrations Life Sci 60 1997 PL115 PL118 9042383
- [21]Borghini I. Barja F. Pometta D. James R.W. Characterization of subpopulations of lipoprotein particles isolated from human cerebrospinal fluid Biochim Biophys Acta 1255 1995 192 200 7696334
- [22]Stukas S. Robert J. Lee M. Kulic I. Carr M. Tourigny K. Intravenously injected human apolipoprotein A-I rapidly enters the central nervous system via the choroid plexus J Am Heart Assoc 3 2014 e001156 25392541 PMC4338702
- [23]Yassine H.N. Feng Q. Chiang J. Petrosspour L.M. Fonteh A.N. Chui H.C. ABCA1-mediated cholesterol efflux capacity to cerebrospinal fluid is reduced in patients with mild cognitive impairment and Alzheimer's disease J Am Heart Assoc 12 2016 e002886 PMC4802440 26873692
- [24]Lenich C. Brecher P. Makrides S. Chobanian A. Zannis V.I. Apolipoprotein gene expression in the rabbit: abundance, size, and distribution of apolipoprotein mRNA species in different tissues J Lipid Res 29 1988 755 764 3171395
- [25]Datta S. Li W.H. Ghosh I. Luo C.C. Chan L. Structure and expression of dog apolipoprotein C-II and C-III mRNAs. Implications for the evolution and functional constraints of apolipoprotein structure J Biol Chem 262 1987 10588 10593 2956259
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Proteome profiling in cerebrospinal fluid reveals novel biomarkers of Alzheimer's disease
Bader, J. M., Geyer, P. E., Müller, J. B., Strauss, M. T., Koch, M., Leypoldt, F., Koertvelyessy, P., Bittner, D., Schipke, C. G., Incesoy, E. I., et al. (2020) · Molecular Systems Biology · doi:10.15252/msb.20199356 · Cited by 286 · see citing works
Self-citationGuo, 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
“800 nM, 47,48 suggesting lipApoE2 minimally engages LDLR in the brain, consistent with Ldlr KO mouse studies.”
High-density lipoprotein-related cholesterol metabolism in Alzheimer's disease
Pedrini, S., Chatterjee, P., Hone, E., & Martins, R. N. (2021) · Journal of Neurochemistry · doi:10.1111/jnc.15170 · Cited by 22 · see citing works
- Authors
- Koch, M., Furtado, J. D., Falk, K., Leypoldt, F., Mukamal, K. J., & Jensen, M. K.
- Affiliations
- Harvard University (US)
- Christian-Albrechts-Universität zu Kiel (DE)
- Beth Israel Deaconess Medical Center (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Koch, Manja
- Venue
- Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
- Publisher
- Wiley
- Published
- 2017-01
- Volume
- 6
- Issue
- 1
- Pages
- 182-187
- ISSN
- 2352-8729 (ISSN-L)
- PMC
- PMC5338868
- OpenAlex
- W2590342394
- Cited by
- 31
- References
- 3
- Citations by year
- 2025: 1 · 2024: 6 · 2023: 2 · 2022: 5 · 2021: 3 · 2020: 8 · 2019: 5 · 2018: 1
- FWCI
- 3.92
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (1R01NS089638‐01A1)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- apolipoproteins, cerebrospinal fluid, plasma apolipoproteins, apolipoprotein A-I, apolipoprotein C-III, apolipoprotein E, clusterin, dementia, biomarkers
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