The DOI matches its Crossref record; 22 of the 22 references it cites were found in a registry or an index.
Isoform‐Specific Effects of Apolipoproteins E2, E3, and E4 on Cerebral Capillary Sequestration and Blood‐Brain Barrier Transport of Circulating Alzheimer's Amyloid β
Abstract
Abstract: Cerebral capillary sequestration and blood‐brain barrier (BBB) permeability to apolipoproteins E2 (apoE2), E3 (apoE3), and E4 (apoE4) and to their complexes with sAβ 1–40, a peptide homologous to the major form of soluble Alzheimer's amyloid β, were studied in perfused guinea pig brain. Cerebrovascular uptake of three apoE isoforms was low, their blood‐to‐brain transport undetectable, but uptake by the choroid plexus significant. Binding of all three isoforms to sAβ 1–40 in vitro was similar with a KD between 11.8 and 12.9 n M. Transport into brain parenchyma and sequestration by BBB and choroid plexus were negligible for sAβ 1–40‐apoE2 and sAβ 1–40‐apoE3, but significant for sAβ 1–40‐apoE4. After 10 min, 85% of sAβ 1–40‐apoE4 taken up at the BBB remained as intact complex, whereas free sAβ 1–40 was 51% degraded. Circulating apoE isoforms have contrasting effects on cerebral capillary uptake of and BBB permeability of sAβ. ApoE2 and apoE3 completely prevent cerebral capillary sequestration and blood‐to‐brain transport of sAβ 1–40. Conversely, apoE4, by entering brain microvessels and parenchyma as a stable complex with sAβ, reduces peptide degradation and may predispose to cerebrovascular and possibly enhance parenchymal amyloid formation under pathological conditions.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“A limited blood brain barrier permeability to circulating lipidpoor apoE2, apoE3, and apoE4 supports that apoE in blood and brain are regulated independently [72,107,108].”
From Plasma levels of apolipoprotein E, APOE genotype and risk of dementia and ischemic heart disease: A review (2016) · cites this paper as [107]
In the citing paper
“Further, previous work suggest a limited blood–brain barrier permeability to circulating lipid-poor apoE,62”
From Plasma levels of apolipoprotein E, APOE genotype, and all-cause and cause-specific mortality in 105 949 individuals from a white general population cohort (2019) · cites this paper as [62]
In the citing paper
“Finally, an apoE4-Aβ complex present in the periphery is sequestered into brain capillaries to a greater extent than Aβ bound to apoE2 or apoE3, demonstrating that apoE4-mediated blood to brain transport of Aβ may play a role in amyloid accumulation in the brain (Martel et al., 1997).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Martel et al., 1997
In the citing paper
“Previous studies from our laboratory and others have demonstrated a major role of the BBB in determining the concentrations of A b in the CNS by regulating transport of circulating A b (33, 39, 49-51, 62-66).”
From Clearance of Alzheimer’s amyloid-β1-40 peptide from brain by LDL receptor–related protein-1 at the blood-brain barrier (2000) · cites this paper as [51]
Citations
Cites
Amyloid plaque core protein in Alzheimer disease and Down syndrome.
Masters, C. L., Simms, G., Weinman, N. A., Multhaup, G., McDonald, B. L., & Beyreuther, K. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.12.4245 · Cited by 4,431
Strittmatter, W. J., Saunders, A. M., Schmechel, D., Pericak-Vance, M., Enghild, J., Salvesen, G. S., & Roses, A. D. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.5.1977 · Cited by 4,268
Isolation and quantification of soluble Alzheimer's β-peptide from biological fluids
Seubert, P., Vigo-Pelfrey, C., Esch, F., Lee, M., Dovey, H., Davis, D., Sinha, S., Schiossmacher, M., Whaley, J., Swindlehurst, C., et al. (1992) · Nature · doi:10.1038/359325a0 · Cited by 1,731
Production of the Alzheimer Amyloid β Protein by Normal Proteolytic Processing
Shoji, M., Golde, T. E., Ghiso, J., Cheung, T. T., Estus, S., Shaffer, L. M., Cai, X.-D., McKay, D. M., Tintner, R., Frangione, B., et al. (1992) · Science · doi:10.1126/science.1439760 · Cited by 1,447
Self-citationApolipoprotein E: Structure-Function Relationships
Weisgraber, K. H. (1994) · Advances in Protein Chemistry · doi:10.1016/s0065-3233(08)60642-7 · Cited by 830
The Pathogenesis of Senile Plaques
DICKSON, D. W. (1997) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199704000-00001 · Cited by 753
Apolipoprotein E, Dementia, and Cortical Deposition of β-Amyloid Protein
Polvikoski, T., Sulkava, R., Haltia, M., Kainulainen, K., Vuorio, A., Verkkoniemi, A., Niinistö, L., Halonen, P., & Kontula, K. (1995) · New England Journal of Medicine · doi:10.1056/nejm199511093331902 · Cited by 493
Strittmatter, W. J., Saunders, A. M., Goedert, M., Weisgraber, K. H., Dong, L. M., Jakes, R., Huang, D. Y., Pericak-Vance, M., Schmechel, D., & Roses, A. D. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.23.11183 · Cited by 474
Triguero, D., Buciak, J. L., & Pardridge, W. M. (1990) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1990.tb04886.x · Cited by 454
Rapid Communication: Characterization of β‐Amyloid Peptide from Human Cerebrospinal Fluid
Vigo‐Pelfrey, C., Lee, D., Keim, P., Lieberburg, I., & Schenk, D. B. (1993) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1993.tb09841.x · Cited by 385
Cited by
Sorted by citations
Items 101–149 of 149
Hypoxia-induced mitochondrial and nuclear DNA damage in the rat brain
Englander, E. W., Greeley, G. H., Wang, G., Perez-Polo, J. R., & Lee, H.-M. (1999) · Journal of Neuroscience Research · doi:10.1002/(sici)1097-4547(19991015)58:2 · Cited by 51
Permeability of the Blood-Brain Barrier to a Rhenacarborane
Hawkins, P. M., Jelliss, P. A., Nonaka, N., Shi, X., & Banks, W. A. (2009) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.108.146878 · Cited by 28
Multifunctional Nanocarriers for Alzheimer’s Disease: Befriending the Barriers
Ansari, M. A., Tripathi, T., Venkidasamy, B., Monziani, A., Rajakumar, G., Alomary, M. N., Alyahya, S. A., Onimus, O., D’souza, N., Barkat, M. A., et al. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03730-z · Cited by 29
Ringland, C., Schweig, J. E., Paris, D., Shackleton, B., Lynch, C., Eisenbaum, M., MULLAN, M. J., Crawford, F., Abdullah, L. I., & Bachmeier, C. J. (2020) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2020.06.018 · Cited by 27
Chroni, A., Pyrpassopoulos, S., Thanassoulas, A., Nounesis, G., Zannis, V. I., & Stratikos, E. (2008) · Biochemistry · doi:10.1021/bi800469r · Cited by 26
Faraji, P., Kühn, H., & Ahmadian, S. (2024) · Journal of Molecular Neuroscience · doi:10.1007/s12031-024-02224-4 · Cited by 25
Sugihara, T., Munesue, S., Yamamoto, Y., Sakurai, S., Akhter, N., Kitamura, Y., Shiba, K., Watanabe, T., Yonekura, H., Hayashi, Y., et al. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-110776 · Cited by 22
O'Callaghan, P. W., Noborn, F., Sehlin, D., Li, J., Lannfelt, L., Lindahl, U., & Zhang, X. (2014) · Amyloid · doi:10.3109/13506129.2013.879643 · Cited by 20
Saini, V., Singh, A., Shukla, R., Jain, K., & Yadav, A. K. (2022) · AAPS PharmSciTech · doi:10.1208/s12249-022-02274-0 · Cited by 19
Apolipoprotein E imbalance in the cerebrospinal fluid of Alzheimer’s disease patients
Lennol, M. P., Sánchez-Domínguez, I., Cuchillo‐Ibáñez, I., Camporesi, E., Brinkmalm, G., Alcolea, D. A., Fortea, J., Lleó, A., Sòria, G., Aguado, F., et al. (2022) · Alzheimer s Research & Therapy · doi:10.1186/s13195-022-01108-2 · Cited by 20
Disordered proteins in dementia
Ingelsson, M., & Hyman, B. T. (2002) · Annals of Medicine · doi:10.1080/078538902320322529 · Cited by 20
Keable, A., O’Neill, R., MacGregor Sharp, M., Gatherer, M., Yuen, H. M., Johnston, D. A., Weller, R. O., & Carare, R. O. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21124371 · Cited by 15
Lipid metabolism in Alzheimer’s and Parkinson’s disease
Xu, Q., & Huang, Y. (2006) · Future Lipidology · doi:10.2217/17460875.1.4.441 · Cited by 16
Road to Alzheimer’s Disease: The Pathomechanism Underlying
Anand, R., Kaushal, A., Wani, W. Y., & Gill, K. D. (2011) · Pathobiology · doi:10.1159/000332218 · Cited by 16
A simple approach for human recombinant apolipoprotein E4 expression and purification
Argyri, L., Skamnaki, V. T., Stratikos, E., & Chroni, A. (2011) · Protein Expression and Purification · doi:10.1016/j.pep.2011.06.011 · Cited by 17
Wang, Y., Xue, Y., Wang, S., Huang, J., & Yang, X. (2020) · Analytical Chemistry · doi:10.1021/acs.analchem.0c03542 · Cited by 14
Role of A β Transport and Clearance in the Pathogenesis and Treatment of Alzheimer’s Disease
Holtzman, D. M., & Zloković, B. V. (2007) · Springer eBooks · doi:10.1007/978-0-387-35135-3_11 · Cited by 15
Nilsson, L. N. G., Gografe, S., Costa, D. A., Hughes, T., Dressler, D., & Potter, H. (2012) · Technology & Innovation · doi:10.3727/194982412x13462021398010 · Cited by 13
Blood–Brain Barrier Transport of Alzheimer’s Amyloid β-Peptide
Nelson, A. R., Sagare, A. P., & Zloković, B. V. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-802173-6.00009-5 · Cited by 12
Poetsch, V., Neuhaus, W., & Noe, C. R. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-090769 · Cited by 11
Bachmeier, C. J., Beaulieu‐Abdelahad, D., MULLAN, M. J., & Paris, D. (2011) · Microcirculation · doi:10.1111/j.1549-8719.2011.00096.x · Cited by 11
Nanomedicine: A New Frontier in Alzheimer’s Disease Drug Targeting
Pathak, K., Ahmad, M. Z., Saikia, R., Pathak, M. P., Sahariah, J. J., Kalita, P., Das, A., Islam, M. A., Pramanik, P., Tayeng, D., et al. (2024) · Central Nervous System Agents in Medicinal Chemistry · doi:10.2174/0118715249281331240325042642 · Cited by 11
Shukla, D., Suryavanshi, A., Bharti, S. K., Asati, V., & Mahapatra, D. K. (2024) · Current Topics in Medicinal Chemistry · doi:10.2174/0115680266299847240328045737 · Cited by 10
DeKroon, R. M., & Armati, P. J. (2002) · Cell Biology International · doi:10.1006/cbir.2002.0868 · Cited by 9
Martins, I. J., Gupta, V. B., Wilson, A. C., Fuller, S. J., & Martins, R. N. (2014) · Current Proteomics · doi:10.2174/157016461103140922163729 · Cited by 7
Decreases in Plasma Aβ1-40 Levels with Aging in Non-Demented Elderly with ApoE-ε4 Allele
Pomara, N., Shao, B., Wısnıewskı, T., & Mehta, P. D. (1998) · Neurochemical Research · doi:10.1023/a:1020936222286 · Cited by 5
Traumatic brain injury and neurodegenerative diseases: the role of axonal injury and amyloid-β
Bi, D., Gao, B., Shen, Y., Dai, Z., Yang, S., & Wang, L. (2025) · Brain Research · doi:10.1016/j.brainres.2025.149873 · Cited by 4
Therapeutics of Alzheimer’s Disease
Herrera-Rivero, M., & Emiliano, G. (2011) · InTech eBooks · doi:10.5772/27990 · Cited by 3
Nanomedicine Based Drug Targeting in Alzheimer’s Disease: High Impact of Small Carter
Ahmad, M. Z., Akhter, S., Rahman, Z., Ahmad, J., Ahmad, I., & Ahmad, F. J. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-803959-5.50016-7 · Cited by 3
Akatsu, H., Kamino, K., Yamagata, H. D., Isojima, D., Kondo, I., Yamamoto, T., Kida, T., Takeda, M., Miki, T., & Kosaka, K. (2004) · Psychogeriatrics · doi:10.1111/j.1479-8301.2004.00058.x · Cited by 4
Li, Q., & Masters, C. L. (2007) · Elsevier eBooks · doi:10.1016/b978-012369367-9/50805-3 · Cited by 2
Vascular Transport of Alzheimer’s Amyloid β Peptides and Apolipoproteins
Zloković, B. V., Ghiso, J. A., & Frangione, B. (2000) · Springer eBooks · doi:10.1007/978-94-017-1007-7_20 · Cited by 1
Self-citationAmyloid Beta and the Cerebral Vasculature
Grammas, P. (2005) · Humana Press eBooks · doi:10.1385/1-59259-824-2:267
Sahni, J. K., Doggui, S., Dao, L. H., & Ramassamy, C. (2011) · Wiley eBooks · doi:10.1002/9780470960844.ch10
Vianna, G. K., Reis, A. E. S., & de Carvalho, L. A. V. (2007) · Summer Computer Simulation Conference · doi:10.5555/1357910.1358031
Eggermont, L. H. P. (2007) · Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam)
Costa, D. A. (2005) · Digital Commons - University of South Florida (University of South Florida)
The role of NPxY domains in LRP1 receptor maturation and function
Pflanzner, T. (2011) · Gutenberg Open Science · doi:10.25358/openscience-3281
V Seminario Internacional de Biopolímeros y Materiales Compuestos sostenibles
Mateo, L. L. (2014) · Revista de plásticos modernos: Ciencia y tecnología de polímeros
Neuropharmacology in Alzheimer and Huntington Disease
Gupta, B., & Rohatgi, K. (2022) · BENTHAM SCIENCE PUBLISHERS eBooks · doi:10.2174/9789815040913122010015
Ringland, C., Schweig, J. E., Eisenbaum, M., Paris, D., Ait‐Ghezala, G., Mullan, M., Crawford, F., Abdullah, L. I., & Bachmeier, C. (2021) · Figshare · doi:10.6084/m9.figshare.14677003
Lennol, M. P., Sánchez-Domínguez, I., Cuchillo‐Ibáñez, I., Camporesi, E., Brinkmalm, G., Alcolea, D. A., Fortea, J., Lleó, A., Sòria, G., Aguado, F., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21485336
Systemic Amyloid-β Metabolism in Alzheimer’s Disease
Dong-yu, F., Wang, J., Gu, B. J., Masters, C. L., & Wang, Y. (2026) · Springer eBooks · doi:10.1007/978-981-95-5222-1_7
OXIDATIVE STRESS ALTERS BLOOD-BRAIN BARRIER INTEGRITY
Lochhead, J. J. (2011) · UA Campus Repository (The University of Arizona)
Cole (2000) · doi:10.1002/1097-0029(20000815)50:4
Self-citationA unifying hypothesis of alzheimer’s disease: III—Risk factors
Heininger, K. (2000) · Human Psychopharmacology: Clinical and Experimental · doi:10.1002/(sici)1099-1077(200001)15:1
Yamauchi (2000) · doi:10.1002/1097-4547(20001115)62:4
(2002) · PubMed · Cited by 24
Metadata
- Authors
- Martel, C. L., Mackic, J. B., Matsubara, E., Governale, S., Miguel, C., Miao, W., McComb, J. G., Frangione, B., Ghiso, J., & Zlokovic, B. V.
- Affiliations
- University of Southern California (US)
- NYU Langone Health (US)
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 1997-11
- Volume
- 69
- Issue
- 5
- Pages
- 1995-2004
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W1974008457
- Cited by
- 149
- References
- 21
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 4 · 2023: 1 · 2022: 4 · 2021: 3 · 2020: 6 · 2019: 5 · 2018: 4 · 2017: 3 · 2016: 6 · 2015: 2 · 2014: 8 · 2013: 3 · 2012: 7
- FWCI
- 4.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS34467)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- apolipoprotein E isoforms, APOE2, APOE3, APOE ε4, blood-brain barrier permeability, amyloid beta degradation, amyloid deposition
- MeSH terms
- Amino Acid Sequence, Animals, Apolipoproteins E, Blood-Brain Barrier, Capillary Permeability, Cerebrovascular Circulation, Female, Guinea Pigs, Humans, Kinetics, Male, Molecular Sequence Data, Peptide Fragments, Perfusion, Recombinant Proteins, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Apolipoprotein E3, Apolipoprotein E4, Apolipoprotein E2
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
