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Amyloid‐β efflux from the central nervous system into the plasma
Abstract
Objective: The aim of this study was to measure the flux of amyloid‐β (Aβ) across the human cerebral capillary bed to determine whether transport into the blood is a significant mechanism of clearance for Aβ produced in the central nervous system (CNS). Methods: Time‐matched blood samples were simultaneously collected from a cerebral vein (including the sigmoid sinus, inferior petrosal sinus, and the internal jugular vein), femoral vein, and radial artery of patients undergoing inferior petrosal sinus sampling. For each plasma sample, Aβ concentration was assessed by 3 assays, and the venous to arterial Aβ concentration ratios were determined. Results: Aβ concentration was increased by ∼7.5% in venous blood leaving the CNS capillary bed compared to arterial blood, indicating efflux from the CNS into the peripheral blood ( p < 0.0001). There was no difference in peripheral venous Aβ concentration compared to arterial blood concentration. Interpretation: Our results are consistent with clearance of CNS‐derived Aβ into the venous blood supply with no increase from a peripheral capillary bed. Modeling these results suggests that direct transport of Aβ across the blood–brain barrier accounts for ∼25% of Aβ clearance, and reabsorption of cerebrospinal fluid Aβ accounts for ∼25% of the total CNS Aβ clearance in humans. Ann Neurol 2014;76:837–844
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“Thus, the neurovascular hypothesis of AD states that Aβ accumulation is driven by impairment of Aβ transporters in brain capillaries, resulting in deficient Aβ elimination via the BBB (3,8,15,16).”
From Endothelial LRP1 transports amyloid-β1–42 across the blood-brain barrier (2015) · cites this paper as [16]
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Cites
The Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864
Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359
Sleep Drives Metabolite Clearance from the Adult Brain
Xie, L., Kang, H., Xu, Q., Chen, M. J., Liao, Y., Thiyagarajan, M., O’Donnell, J., Christensen, D. J., Nicholson, C., Iliff, J. J., et al. (2013) · Science · doi:10.1126/science.1241224 · Cited by 5,411
Scheuner, D., Eckman, C., Jensen, M., Song, X., Citron, M., Suzuki, N., Bird, T. D., Hardy, J., Hutton, M., Kukull, W., et al. (1996) · Nature Medicine · doi:10.1038/nm0896-864 · Cited by 2,599
Decreased Clearance of CNS β-Amyloid in Alzheimer’s Disease
Mawuenyega, K. G., Sigurdson, W., Ovod, V., Munsell, L., Kasten, T., Morris, J. C., Yarasheski, K. E., & Bateman, R. J. (2010) · Science · doi:10.1126/science.1197623 · Cited by 2,078
Self-citationCerebrospinal fluid and plasma biomarkers in Alzheimer disease
Blennow, K., Hampel, H., Weiner, M., & Zetterberg, H. (2010) · Nature Reviews Neurology · doi:10.1038/nrneurol.2010.4 · Cited by 1,863
RAGE mediates amyloid-β peptide transport across the blood-brain barrier and accumulation in brain
Deane, R., Du Yan, S., Submamaryan, R. K., LaRue, B., Jovanovic, S., Hogg, E., Welch, D., Manness, L., Lin, C., Yu, J., et al. (2003) · Nature Medicine · doi:10.1038/nm890 · Cited by 1,426
DeMattos, R. B., Bales, K. R., Cummins, D. J., Dodart, J.-C., Paul, S. M., & Holtzman, D. M. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.151261398 · Cited by 1,298
Plasma and Cerebrospinal Fluid Levels of Amyloid β Proteins 1-40 and 1-42 in Alzheimer Disease
Mehta, P. D., Pirttilä, T., Mehta, S. P., Sersen, E. A., Aisen, P. S., & Wisniewski, H. M. (2000) · Archives of Neurology · doi:10.1001/archneur.57.1.100 · Cited by 582
Wang, J., Dickson, D. W., Trojanowski, J. Q., & Lee, V. M.-Y. (1999) · Experimental Neurology · doi:10.1006/exnr.1999.7085 · Cited by 567
Research works printed but not linked: 31
- 10.1212/WNL.35.7.957 · DOI · Paper page
- 10.1016/j.drudis.2006.08.004 · DOI
- 10.1111/j.1471-4159.2004.02385.x · DOI · Paper page
- 10.2174/187152709787601867 · DOI
- 10.1212/01.wnl.0000306696.82017.66 · DOI
- 10.1016/0024-3205(94)00331-9 · DOI · Paper page
- 10.1016/j.neuron.2012.10.029 · DOI · Paper page
- 10.1016/j.neuron.2004.07.017 · DOI · Paper page
- 10.1056/NEJM199109263251301 · DOI
- 10.1016/j.jasms.2007.02.009 · DOI
- 10.1038/nm1438 · DOI · Paper page
- Okereke OI, 2009, Performance characteristics of plasma amyloid‐beta 40 and 42 assays, J Alzheimers Dis, 16, 277, 10.3233/JAD-2009-0948 · DOI
- 10.1016/j.brainres.2012.02.041 · DOI
- 10.1007/s002920050040 · DOI
- 10.1152/ajpheart.00658.2011 · DOI
- 10.1016/j.jcmg.2011.09.026 · DOI
- 10.1063/1.4819067 · DOI
- 10.1152/ajpendo.00489.2003 · DOI
- 10.1136/bmjopen-2013-004250 · DOI
- 10.3233/JAD-2011-111328 · DOI
- 10.1212/01.wnl.0000256043.50901.e3 · DOI · Paper page
- 10.1073/pnas.83.4.1140 · DOI · Paper page
- 10.1016/j.neurobiolaging.2008.03.027 · DOI
- 10.1016/S0304-3940(01)01754-2 · DOI
- 10.1126/science.1067568 · DOI · Paper page
- 10.1007/s11538-010-9540-5 · DOI
- Banks WA, 2011, Impairments in brain‐to‐blood transport of amyloid‐beta and reabsorption of cerebrospinal fluid in an animal model of Alzheimer's disease are reversed by antisense directed against amyloid‐beta protein precursor, J Alzheimers Dis, 23, 599, 10.3233/JAD-2010-100021 · DOI
- 10.1007/s11064-010-0374-1 · DOI
- Bjerke M, 2010, Confounding factors influencing amyloid Beta concentration in cerebrospinal fluid, Int J Alzheimers Dis, 2010
- 10.1186/1743-8454-5-10 · DOI · Paper page
- Hurley PJ, 1975, Red cell and plasma volumes in normal adults, J Nucl Med, 16, 46
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Ovod, V., Ramsey, K. N., Mawuenyega, K. G., Bollinger, J. G., Hicks, T., Schneider, T., Sullivan, M., Paumier, K., Holtzman, D. M., Morris, J. C., et al. (2017) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2017.06.2266 · Cited by 585
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Storck, S. E., Meister, S., Nahrath, J., Meißner, J. N., Schubert, N., Di Spiezio, A., Baches, S., Vandenbroucke, R. E., Bouter, Y., Prikulis, I., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci81108 · Cited by 477
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Self-citationMa, Q., Zhao, Z., Sagare, A. P., Wu, Y., Wang, M., Owens, N. C., Verghese, P. B., Herz, J., Holtzman, D. M., & Zlokovic, B. V. (2018) · Molecular Neurodegeneration · doi:10.1186/s13024-018-0286-0 · Cited by 281
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“However, evidence indicates that impaired clearance is mainly responsible (Bateman et al., 2006; Roberts et al., 2014).”
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Boada, M., López, O., Núñez, L., Szczepiorkowski, Z. M., Torres, M., Grifols, C., & Páez, A. (2019) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1016/j.trci.2019.01.001 · Cited by 91
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Self-citationZhao, Z., Liu, Y., Ruan, S., & Hu, Y. (2023) · International Journal of Nanomedicine · doi:10.2147/ijn.s444115 · Cited by 49
Reduced Cardiovascular Functions in Patients with Alzheimer’s Disease
Jin, W.-S., Bu, X.-L., Wang, Y.-R., Li, L., Li, W.-W., Liu, Y.-H., Zhu, C., Yao, X.-Q., Chen, Y., Gao, C.-Y., et al. (2017) · Journal of Alzheimer's Disease · doi:10.3233/jad-170088 · Cited by 27
Metadata
- Authors
- Roberts, K. F., Elbert, D. L., Kasten, T. P., Patterson, B. W., Sigurdson, W. C., Connors, R. E., Ovod, V., Munsell, L. Y., Mawuenyega, K. G., Miller‐Thomas, M. M., Moran, C. J., Cross, D. T., Derdeyn, C. P., & Bateman, R. J.
- Affiliations
- Department of Neurology Washington University School of Medicine St Louis MO
- Department of Biomedical Engineering Washington University in St Louis St Louis MO
- Departments of Medicine Washington University School of Medicine St Louis MO
- Departments of Radiology Washington University School of Medicine St Louis MO
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2014-10-24
- Volume
- 76
- Issue
- 6
- Pages
- 837-844
- ISSN
- 0364-5134
- 1531-8249
- PMC
- PMC4355962
- Cited by
- 254
- References
- 17
- Language
- en
- Funders
- National Institutes of Health (R01NS065667)
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