The DOI matches its Crossref record; 70 of the 71 references it cites were found in a registry or an index.
apoE isoform–specific disruption of amyloid β peptide clearance from mouse brain
Open accessAbstract
Neurotoxic amyloid beta peptide (Abeta) accumulates in the brains of individuals with Alzheimer disease (AD). The APOE4 allele is a major risk factor for sporadic AD and has been associated with increased brain parenchymal and vascular amyloid burden. How apoE isoforms influence Abeta accumulation in the brain has, however, remained unclear. Here, we have shown that apoE disrupts Abeta clearance across the mouse blood-brain barrier (BBB) in an isoform-specific manner (specifically, apoE4 had a greater disruptive effect than either apoE3 or apoE2). Abeta binding to apoE4 redirected the rapid clearance of free Abeta40/42 from the LDL receptor-related protein 1 (LRP1) to the VLDL receptor (VLDLR), which internalized apoE4 and Abeta-apoE4 complexes at the BBB more slowly than LRP1. In contrast, apoE2 and apoE3 as well as Abeta-apoE2 and Abeta-apoE3 complexes were cleared at the BBB via both VLDLR and LRP1 at a substantially faster rate than Abeta-apoE4 complexes. Astrocyte-secreted lipo-apoE2, lipo-apoE3, and lipo-apoE4 as well as their complexes with Abeta were cleared at the BBB by mechanisms similar to those of their respective lipid-poor isoforms but at 2- to 3-fold slower rates. Thus, apoE isoforms differentially regulate Abeta clearance from the brain, and this might contribute to the effects of APOE genotype on the disease process in both individuals with AD and animal models of AD.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Using homozygous human APOE knock-in mice, previous work demonstrated that APOE4 promotes A β aggregation and impairs its clearance relative to APOE3 34,38,39 .”
From APOE2 attenuates APOE4-associated amyloid pathology and related toxicity in a mouse model of Alzheimer’s disease (2026) · cites this paper as [39]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“APOE exerts toxic effects on the cerebrovascular system (694) and neurons (383, 384) and influences A 𝛃 clearance (60, 64, 98, 135, 256, 266, 278, 294, 315, 693), amyloid deposition (39, 256, 258, 266, 278, 314, 518, 612), and tau-related neurodegeneration (533) in an allele-dependent manner APOE4 > APOE3 > APOE2 .”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [135]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In fact increased rate of soluble Aβ clearance across the BBB has been experimentally confirmed in the setting of the APOE ε2 allele [32, 48].”
From APOE Genotype Differentially Modulates Effects of Anti-Aβ, Passive Immunization in APP Transgenic Mice (2017) · cites this paper as [48]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Notably, the contribution of ISF bulk flow to total Aβ clearance was minimal (Fig. 1B), consistent with previous studies (14, 15, 20).”
From Low-density lipoprotein receptor overexpression enhances the rate of brain-to-blood Aβ clearance in a mouse model of β-amyloidosis (2012) · cites this paper as [15]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“When injecting low nM [ 125 I] Aβ 1-42 concentrations in mice, we found no significant amount of radioactivity in the CSF, showing that the small amounts of injected Aβ are rapidly cleared via the BBB and that a minor amount of injected Aβ is cleared via bulk flow as also observed by previous studies (8,11,12).”
From Endothelial LRP1 transports amyloid-β1–42 across the blood-brain barrier (2015) · cites this paper as [12]
Experimental — accuracy not yet measured
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Moreover, with an endocytosis rate up to 16 times faster than that of other Aβ receptors, such as VDLDR or LDLR (12,35), LRP1 may outperform other receptors in Aβ clearance, especially at higher concentrations.”
From Endothelial LRP1 transports amyloid-β1–42 across the blood-brain barrier (2015) · cites this paper as [12]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Moreover, with an endocytosis rate up to 16 times faster than that of other Aβ receptors, such as VDLDR or LDLR (12,35), LRP1 may outperform other receptors in Aβ clearance, especially at higher concentrations.”
From Endothelial LRP1 transports amyloid-β1–42 across the blood-brain barrier (2015) · cites this paper as [12]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“LRP1 also binds APOE2 and APOE3 as well as APOE2-A 𝛃 and APOE3-A 𝛃 complexes at the abluminal side of the BBB, mediating their efflux from brain-toblood (135).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [135]
The cited source says what the claim attributes to it.
In the citing paper
“Studies in animal models support that APOE4 compared with APOE3 and APOE2 diminishes A 𝛃 clearance across the BBB (58, 135), which has been confirmed in transgenic APOE4 mice (98).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [135]
The cited source says what the claim attributes to it.
In the citing paper
“and in animal models, APOE4 compared with APOE3 and APOE2 leads to impaired clearance of A 𝛃 across the BBB (58, 98, 135) and an early BBB breakdown and transporters' dysregulation (9, 60, 85, 437).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [135]
The cited source says what the claim attributes to it.
In the citing paper
“A recent study wherein apoE/Aβ complexes were microinjected into wildtype mouse brain revealed that Aβ bound to apoE4 is cleared more slowly than when Aβ is complexed to apoE3 or apoE2 (56).”
From Human ApoE isoforms differentially regulate brain amyloid-β peptide clearance (2011) · cites this paper as [56]
The cited source says what the claim attributes to it.
In the citing paper
“Several studies demonstrated that apoE isoforms can differentially affect Aβ clearance (Deane et al., 2008; Jiang et al., 2008; Castellano et al., 2011).”
From Haploinsufficiency of Human APOE Reduces Amyloid Deposition in a Mouse Model of Amyloid-β Amyloidosis (2011) · cites this paper as Deane et al., 2008
The cited source says what the claim attributes to it.
In the citing paper
“Furthermore, recent studies strongly suggest that apoE regulates both extracellular and intracellular Aβ clearance in the brain (Bell et al., 2007; Deane et al., 2008; DeMattos et al., 2004; Jiang et al., 2008).”
From Overexpression of Low-Density Lipoprotein Receptor in the Brain Markedly Inhibits Amyloid Deposition and Increases Extracellular Aβ Clearance (2009) · cites this paper as Deane et al., 2008
The cited source says what the claim attributes to it.
In the citing paper
“Furthermore, apoE has been shown to regulate Aβ clearance in the brain (Bell et al., 2007; Deane et al., 2008; DeMattos et al., 2004; Jiang et al., 2008).”
From Overexpression of Low-Density Lipoprotein Receptor in the Brain Markedly Inhibits Amyloid Deposition and Increases Extracellular Aβ Clearance (2009) · cites this paper as Deane et al., 2008
The cited source says what the claim attributes to it.
In the citing paper
“Furthermore, Aβ complexed to apoE2 and apoE3 is cleared out of the brain at a significantly faster rate than Aβ complexed to apoE4 (Deane et al., 2008).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Deane et al., 2008
The cited source says what the claim attributes to it.
In the citing paper
“A recent study has shown that the brain to blood clearance of lipidated apoE4 in the mouse brain is significantly lower than the clearance of apoE3 and apoE2 (Deane et al., 2008).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Deane et al., 2008
The cited source says what the claim attributes to it.
In the citing paper
“Accumulating recent evidence strongly suggests that when human apoE is complexed with Aβ, the brain to blood clearance of Aβ is actually decreased compared to that of free Aβ (Bell et al., 2007; Deane et al., 2008; Ito et al., 2007).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Deane et al., 2008
The cited source says what the claim attributes to it.
In the citing paper
“In animal models, Aβ–ApoE2 and Aβ–ApoE3 complexes are cleared by the blood brain barrier (BBB) at a substantially higher rate than Aβ–ApoE4 complexes [23].”
From The new genetic landscape of Alzheimer’s disease: from amyloid cascade to genetically driven synaptic failure hypothesis? (2019) · cites this paper as [23]
The cited source says what the claim attributes to it.
In the citing paper
“These results suggest the LDLR overexpression in neurons and astrocytes (18) likely increases BBB-mediated Aβ clearance through an indirect mechanism involving other apoE receptors at the BBB, such as LRP1—a receptor shown to directly mediate Aβ clearance across the BBB (14, 15, 26).”
From Low-density lipoprotein receptor overexpression enhances the rate of brain-to-blood Aβ clearance in a mouse model of β-amyloidosis (2012) · cites this paper as [15]
The cited source says what the claim attributes to it.
In the citing paper
“our work strongly suggests that LDLR influences Aβ metabolism by affecting its clearance from the brain into blood, a mechanism previously suggested only for LRP1 and VLDLR (13–15, 26).”
From Low-density lipoprotein receptor overexpression enhances the rate of brain-to-blood Aβ clearance in a mouse model of β-amyloidosis (2012) · cites this paper as [15]
The cited source says what the claim attributes to it.
In the citing paper
“Although low-density lipoprotein receptor-related protein 1 (LRP1) has been well characterized for its role in BBB-mediated Aβ clearance (13–15), whether LDLR plays a role in Aβ clearance across the BBB is unclear.”
From Low-density lipoprotein receptor overexpression enhances the rate of brain-to-blood Aβ clearance in a mouse model of β-amyloidosis (2012) · cites this paper as [15]
The cited source says what the claim attributes to it.
In the citing paper
“ApoE has been shown to impede the clearance of Aβ from brain ISF (13, 15, 43); therefore, it is likely that the reduction of apoE levels with LDLR overexpression facilitates greater ISF Aβ clearance across the BBB.”
From Low-density lipoprotein receptor overexpression enhances the rate of brain-to-blood Aβ clearance in a mouse model of β-amyloidosis (2012) · cites this paper as [15]
The cited source says what the claim attributes to it.
In the citing paper
“Recent studies suggest that transport across the BBB is a major elimination route for brain Aβ (8,11,12,15).”
From Endothelial LRP1 transports amyloid-β1–42 across the blood-brain barrier (2015) · cites this paper as [12]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“However, levels of apoE in human cerebrospinal fluid do display genotype-dependent pattern similar to the pattern in plasma, further murine interstitial fluid was observed to have genotype-dependent apoE levels similar to the pattern in cerebrospinal fluid [105,112,113].”
From Plasma levels of apolipoprotein E, APOE genotype and risk of dementia and ischemic heart disease: A review (2016) · cites this paper as [113]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“However, levels of apoE in human cerebrospinal fluid do display genotype-dependent pattern similar to the pattern in plasma, further murine interstitial fluid was observed to have genotype-dependent apoE levels similar to the pattern in cerebrospinal fluid [105,112,113].”
From Plasma levels of apolipoprotein E, APOE genotype and risk of dementia and ischemic heart disease: A review (2016) · cites this paper as [113]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
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
Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptide
Haass, C., & Selkoe, D. J. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2101 · Cited by 4,744
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
The Blood-Brain Barrier in Health and Chronic Neurodegenerative Disorders
Zlokovic, B. V. (2008) · Neuron · doi:10.1016/j.neuron.2008.01.003 · Cited by 3,280
Neurovascular regulation in the normal brain and in Alzheimer's disease
Iadecola, C. (2004) · Nature Reviews Neuroscience · doi:10.1038/nrn1387 · Cited by 2,213
Tau Suppression in a Neurodegenerative Mouse Model Improves Memory Function
SantaCruz, K., Lewis, J., Spires, T., Paulson, J., Kotilinek, L., Ingelsson, M., Guimaraes, A., DeTure, M., Ramsden, M., McGowan, E., et al. (2005) · Science · doi:10.1126/science.1113694 · Cited by 2,014
Regulation of NMDA receptor trafficking by amyloid-β
Snyder, E. M., Nong, Y., Almeida, C. G., Paul, S., Moran, T., Choi, E. Y., Nairn, A. C., Salter, M. W., Lombroso, P. J., Gouras, G. K., et al. (2005) · Nature Neuroscience · doi:10.1038/nn1503 · Cited by 1,561 · cited 1×
“Clearance of Alzheimer’s amyloid β(1-40)-peptide from brain by LDL receptor-related protein-1 at the blood-brain barrier.”
BackgroundA68: a Major Subunit of Paired Helical Filaments and Derivatized Forms of Normal Tau
Lee, V. M.-Y., Balin, B. J., Otvos, L., & Trojanowski, J. Q. (1991) · Science · doi:10.1126/science.1899488 · Cited by 1,418 · cited 1×
“Clearance of Alzheimer’s amyloid β(1-40)-peptide from brain by LDL receptor-related protein-1 at the blood-brain barrier.”
BackgroundShibata, M., Yamada, S., Kumar, S. R., Calero, M., Bading, J., Frangione, B., Holtzman, D. M., Miller, C. A., Strickland, D. K., Ghiso, J., et al. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10498 · Cited by 1,413
Self-citationRovelet‐Lecrux, A., Hannequin, D., Raux, G., Meur, N. L., Laquerrière, A., Vital, A., Dumanchin‐Njock, C., Feuillette, S., Brice, A., Vercelletto, M., et al. (2005) · Nature Genetics · doi:10.1038/ng1718 · Cited by 1,284
Flagged first, then by citations
1 of the 71 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- Tanzi, 2004, Neuron., 43, 605
- 10.1042/0264-6021:3480359 · DOI · Paper page
Cited by
Sorted by citations
Items 401–500 of 767
Lim, W. L. F., Lam, S. M., Shui, G., Mondal, A., Ong, D., Duan, X., Creegan, R., Martins, I. J., Sharman, M. J., Taddei, K., et al. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.03.012 · Cited by 37
Diet and Age Interactions with Regards to Cholesterol Regulation and Brain Pathogenesis
Uranga, R. M., & Keller, J. N. (2010) · Current Gerontology and Geriatrics Research · doi:10.1155/2010/219683 · Cited by 36
Regulation of cholesterol efflux by amyloid β secretion
Umeda, T., Mori, H., Zheng, H., & Tomiyama, T. (2010) · Journal of Neuroscience Research · doi:10.1002/jnr.22360 · Cited by 34
Mitochondrial mechanisms in amyloid beta peptide-induced cerebrovascular degeneration
Hsu, M., Sheu, J., Lin, C., Shen, M., & Hsu, C. Y. (2009) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2009.08.003 · Cited by 34
APOE2 mitigates disease-related phenotypes in an isogenic hiPSC-based model of Alzheimer’s disease
Brookhouser, N., Raman, S., Frisch, C., Srinivasan, G., & Brafman, D. A. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01076-3 · Cited by 33
Apolipoprotein E Regulates Injury-Induced Activation of Hippocampal Neural Stem and Progenitor Cells
Hong, S. J., Washington, P. M., Kim, A., Yang, C.-P., Yu, T., & Kernie, S. G. (2015) · Journal of Neurotrauma · doi:10.1089/neu.2014.3860 · Cited by 33
Li, Y., Liu, L., Ji, W., Peng, H., Zhao, R., & Zhang, X. (2020) · Nano Today · doi:10.1016/j.nantod.2020.101006 · Cited by 34
Fote, G. M., Geller, N. R., Efstathiou, N. E., Hendricks, N., Vavvas, D. G., Reidling, J. C., Thompson, L. M., & Steffan, J. S. (2022) · Journal of Cell Science · doi:10.1242/jcs.258687 · Cited by 36
Lane, R. F., Shineman, D. W., Steele, J., Lee, L. H., & Fillit, H. M. (2012) · Advances in pharmacology · doi:10.1016/b978-0-12-394816-8.00007-6 · Cited by 35
Genetic variants associated with neurodegenerative Alzheimer disease in natural models
Salazar, C., Valdivia, G., Ardiles, Á. O., Ewer, J., & Palacios, A. G. (2016) · Biological Research · doi:10.1186/s40659-016-0072-9 · Cited by 33
Preman, P., Moechars, D., Fertan, E., Wolfs, L., Serneels, L., Shah, D., Lamote, J., Poovathingal, S., Snellinx, A., Mancuso, R., et al. (2024) · EMBO Molecular Medicine · doi:10.1038/s44321-024-00162-7 · Cited by 32
New insights into the role of fibroblast growth factors in Alzheimer’s disease
Alam, R., Mrad, Y., Hammoud, H., Saker, Z., Fares, Y., Estephan, E., Bahmad, H. F., Harati, H., & Nabha, S. M. (2021) · Molecular Biology Reports · doi:10.1007/s11033-021-06890-0 · Cited by 32
Thal, D. R. (2009) · The Scientific World JOURNAL · doi:10.1100/tsw.2009.72 · Cited by 32
Metabolite Clearance During Wakefulness and Sleep
Hladky, S. B., & Barrand, M. A. (2017) · Handbook of experimental pharmacology · doi:10.1007/164_2017_37 · Cited by 36
The Blood-Brain Barrier in Alzheimer’s Disease
Storck, S. E., Hartz, A. M. S., & Pietrzik, C. U. (2020) · Handbook of experimental pharmacology · doi:10.1007/164_2020_418 · Cited by 31
Teng, E., Chow, N., Hwang, K., Thompson, P. M., Gylys, K. H., Cole, G. M., Jack, C. R., Shaw, L. M. J., Trojanowski, J. Q., Soares, H. D., et al. (2014) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000368982 · Cited by 33
McFall, G. P., Wiebe, S. A., Vergote, D., Westaway, D. A., Jhamandas, J. H., Bäckman, L., & Dixon, R. A. (2014) · Neuropsychology · doi:10.1037/neu0000150 · Cited by 32
Zhu, C., Wong, M., Li, Q., Sawrey‐Kubicek, L., Beals, E., Rhodes, C. H., Sacchi, R., Lebrilla, C. B., & Zivkovic, A. M. (2019) · Journal of Proteome Research · doi:10.1021/acs.jproteome.9b00450 · Cited by 33
Opposing Roles of apolipoprotein E in aging and neurodegeneration
Hudry, E., Klickstein, J., Cannavo, C., Jackson, R., Muzikansky, A., Gandhi, S., Urick, D., Sargent, T., Wrobleski, L., Roe, A. D., et al. (2019) · Life Science Alliance · doi:10.26508/lsa.201900325 · Cited by 30
Alzheimer’s Disease Etiology Hypotheses and Therapeutic Strategies: A Perspective
Scarano, N., Musumeci, F., Casini, B., Brullo, C., D’Ursi, P., Fossa, P., Schenone, S., & Cichero, E. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26146980 · Cited by 32
Jing, B., Zhang, C., Liu, X., Zhou, L., Liu, J., Yao, Y., Yu, J., Weng, Y., Pan, M., Liu, J., et al. (2017) · Protein & Cell · doi:10.1007/s13238-017-0449-8 · Cited by 32
Wang, X., Li, H., Sheng, Y., He, B., Liu, Z., Li, W., Yu, S., Wang, J., Zhang, Y., Chen, J., et al. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.116071 · Cited by 29
The therapeutic potential of probucol and probucol analogues in neurodegenerative diseases
Sharif, A., Mamo, J. C. L., Lam, V., Al‐Salami, H., Mooranian, A., Watts, G. F., Clarnette, R., Luna, G., & Takechi, R. (2024) · Translational Neurodegeneration · doi:10.1186/s40035-024-00398-w · Cited by 29
Ojo, J. O., Reed, J. M., Crynen, G. C., Vallabhaneni, P., Evans, J., Shackleton, B., Eisenbaum, M., Ringland, C., Edsell, A., MULLAN, M. J., et al. (2021) · Molecular Brain · doi:10.1186/s13041-021-00803-9 · Cited by 30
Kisler, K., Sagare, A. P., Lazić, D., Bazzi, S. A., Lawson, E. J., Hsu, C.-J., Wang, Y., Ramanathan, A., Nelson, A. R., Zhao, Z., et al. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00597-5 · Cited by 29
Self-citationBody fluid biomarkers in Alzheimer's disease.
Lu, H., Zhu, X., Jiang, T., Yu, J., & Tan, L. (2015) · PubMed Central · doi:10.3978/j.issn.2305-5839.2015.02.13 · Cited by 29
Mapping ApoE/Aβ binding regions to guide inhibitor discovery
Liu, Q. R., Wu, W., Fang, C.-L., Li, R., Liu, P., Lei, P., Hu, J., Sun, X., Zheng, Y.-Z., Zhao, Y., et al. (2011) · Molecular BioSystems · doi:10.1039/c1mb05019b · Cited by 29
Jha, N. K., Kar, R., & Niranjan, R. (2019) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026619666190412121811 · Cited by 30
Zeng, B., Zhao, G., & Liu, H. L. (2020) · Neuroscience · doi:10.1016/j.neuroscience.2020.01.005 · Cited by 30
APOE and mild cognitive impairment: the Framingham Heart Study
Jefferson, A. L., Beiser, A., Seshadri, S. S., Wolf, P. A., & Au, R. (2014) · Age and Ageing · doi:10.1093/ageing/afu183 · Cited by 28
Muza, P. M., Bachmeier, C. J., Mouzon, B., Algamal, M., Rafi, N. G., Lungmus, C., Abdullah, L. I., Evans, J. E., Ferguson, S., MULLAN, M. J., et al. (2019) · Neuroscience · doi:10.1016/j.neuroscience.2019.01.049 · Cited by 28
How does the brain remove its waste metabolites from within?
Cheng, Y., & Haorah, J. (2019) · PubMed Central · Cited by 28
Are apolipoprotein E fragments a promising new therapeutic target for Alzheimer’s disease?
Vecchio, F. L., Bisceglia, P., Imbimbo, B. P., Lozupone, M., Latino, R. R., Resta, E., Leone, M., Solfrizzi, V., Greco, A., Daniele, A., et al. (2022) · Therapeutic Advances in Chronic Disease · doi:10.1177/20406223221081605 · Cited by 28
Shanthi, K. B., Krishnan, S., & Rani, P. (2015) · SAGE Open Medicine · doi:10.1177/2050312115598250 · Cited by 29
Basak, J. M., Kim, J., Pyatkivskyy, Y., Wildsmith, K. R., Jiang, H., Parsadanian, M., Patterson, B. W., Bateman, R. J., & Holtzman, D. M. (2012) · Molecular Neurodegeneration · doi:10.1186/1750-1326-7-14 · Cited by 27
Self-citationApoA1, ApoJ and ApoE Plasma Levels and Genotype Frequencies in Cerebral Amyloid Angiopathy
Montañola, A., de Retana, S. F., López‐Rueda, A., Merino-Zamorano, C., Peñalba, A., Fernández‐Álvarez, P., Rodríguez‐Luna, D., Malagelada, A., Pujadas, F., Montaner, J., et al. (2015) · NeuroMolecular Medicine · doi:10.1007/s12017-015-8381-7 · Cited by 29
Dorey, E., Bamji‐Mirza, M., Najem, D., Li, Y., Liu, H., Callaghan, D., Walker, D. G., Lue, L., Stanimirovic, D. B., & Zhang, W. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-160133 · Cited by 28
Pahnke, J., Bascuñana, P., Brackhan, M., Stefan, K., Namasivayam, V., Koldamova, R. P., Wu, J., Möhle, L., & Stefan, S. M. (2021) · Free Neuropathology · doi:10.17879/freeneuropathology-2021-3528 · Cited by 29
Agyare, E. K., Leonard, S. R., Curran, G. L., Yu, C. C., Lowe, V. J., Paravastu, A. K., Poduslo, J. F., & Kandimalla, K. K. (2012) · Molecular Pharmaceutics · doi:10.1021/mp300352c · Cited by 27
Li, W., Chen, C., Xu, B., Chen, J., Yang, M., Gao, L., & Zhou, J. (2024) · Biochemical Pharmacology · doi:10.1016/j.bcp.2024.116643 · Cited by 27
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
Blood lipid markers are associated with hippocampal viscoelastic properties and memory in humans
Sanjana, F., Delgorio, P. L., Hiscox, L. V., DeConne, T. M., Hobson, J. C., Cohen, M. L., Johnson, C. L., & Martens, C. R. (2020) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x20968032 · Cited by 28
de Frutos‐Lucas, J., Sewell, K. R., García‐Colomo, A., Markovic, S. J., Erickson, K. I., & Brown, B. M. (2023) · Alzheimer s Research & Therapy · doi:10.1186/s13195-023-01170-4 · Cited by 26
Sun, R., Feng, J., & Wang, J. (2023) · Aging and Disease · doi:10.14336/ad.2023.0621 · Cited by 28
Chapter 7 Cell Protective Functions of Secretory Clusterin (sCLU)
Klock, G., Baiersdörfer, M., & Koch-Brandt, C. (2009) · Advances in cancer research · doi:10.1016/s0065-230x(09)04007-x · Cited by 27
Alzheimer's dementia by circulation disorders: when trees hide the forest
Dotti, C. G., & Strooper, B. D. (2009) · Nature Cell Biology · doi:10.1038/ncb0209-114 · Cited by 30
Light chain amyloidosis: Where are the light chains from and how they play their pathogenic role?
Zhang, C., Huang, X., & Li, J. (2017) · Blood Reviews · doi:10.1016/j.blre.2017.03.002 · Cited by 26
Modified Glutamatergic Postsynapse in Neurodegenerative Disorders
Moraes, B. J., Coelho, P., Fão, L., Ferreira, I. L., & Rego, A. C. (2019) · Neuroscience · doi:10.1016/j.neuroscience.2019.12.002 · Cited by 27
Potential importance of B cells in aging and aging-associated neurodegenerative diseases
Biragyn, A., Aliseychik, M., & Rogaev, E. (2017) · Seminars in Immunopathology · doi:10.1007/s00281-016-0615-8 · Cited by 25
Fareed, M. M., Qasmi, M., Aziz, S., Völker, E., Förster, C. Y., & Shityakov, S. (2022) · Biomolecules · doi:10.3390/biom12101452 · Cited by 25
Cross interactions between Apolipoprotein E and amyloid proteins in neurodegenerative diseases
Loch, R. A., Wang, H., Perálvarez‐Marín, A., Berger, P., Nielsen, H. M., Chroni, A., & Luo, J. (2023) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2023.01.022 · Cited by 26
Koudinov, A. R., Kezlya, E., Koudinova, N. V., & Berezov, T. T. (2009) · Journal of Alzheimer s Disease · doi:10.3233/jad-2009-1202 · Cited by 25
Animal Models of Alzheimer’s Disease
Newman, M., Kretzschmar, D., Khan, I., Chen, M., Verdile, G., & Lardelli, M. T. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-809468-6.00040-1 · Cited by 25
Okoro, E. U. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22126236 · Cited by 18
Role of Syndecans in Lipid Metabolism and Human Diseases
Леонова, Е. И., & Galzitskaya, O. V. (2015) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-17344-3_10 · Cited by 26
Medoro, A., Bartollino, S., Mignogna, D., Passarella, D., Porcile, C., Pagano, A., Florio, T., Nizzari, M., Guerra, G., Marco, R. D., et al. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-170628 · Cited by 25
Pallebage‐Gamarallage, M. M., Takechi, R., Lam, V., Galloway, S., Dhaliwal, S. S., & Mamo, J. C. L. (2010) · Atherosclerosis Supplements · doi:10.1016/j.atherosclerosissup.2010.04.002 · Cited by 24
Sakai, K., Tiebel, O., Ljungberg, M. C., Sullivan, M., Lee, H.-J., Terashima, T., Li, R., Kobayashi, K., Lu, H.-C., Chan, L., et al. (2009) · Brain Research · doi:10.1016/j.brainres.2009.04.030 · Cited by 23
APOE4 impairs autophagy and Aβ clearance by microglial cells
Bassal, R., Rivkin-Natan, M., Rabinovich, A., Michaelson, D. M., Frenkel, D., & Pinkas-Kramarski, R. (2025) · Inflammation Research · doi:10.1007/s00011-025-02016-5 · Cited by 23
Grangeon, L., Quesney, G., Verdalle-Cazes, M., Coulette, S., Renard, D., Wacongne, A., Allou, T., Olivier, N., Boukriche, Y., Blanchet-Fourcade, G., et al. (2022) · Journal of Neurology · doi:10.1007/s00415-022-11145-4 · Cited by 23
Lipid Dys-Homeostasis Contributes to APOE4-Associated AD Pathology
Lazar, A. N., Hanbouch, L., Boussicaut, L., Fourmaux, B., Daira, P., Millan, M. J., Bernoud‐Hubac, N., & Potier, M. (2022) · Cells · doi:10.3390/cells11223616 · Cited by 23
Ruzali, W. A. W., Kehoe, P. G., & Love, S. (2012) · Neuroscience Letters · doi:10.1016/j.neulet.2012.07.065 · Cited by 25
Kimpe, L. D., & Scheper, W. (2009) · Current Medicinal Chemistry · doi:10.2174/092986710790149765 · Cited by 23
Zepa, L., Frenkel, M., Belinson, H., Kariv-Inbal, Z., Kayed, R., Masliah, E., & Michaelson, D. M. (2011) · International Journal of Alzheimer’s Disease · doi:10.4061/2011/792070 · Cited by 23
Mural Cells: Potential Therapeutic Targets to Bridge Cardiovascular Disease and Neurodegeneration
Lin, A., Peiris, N. J., Dhaliwal, H., Hakim, M., Li, W., Ganesh, S., Ramaswamy, Y., Patel, S., & Misra, A. (2021) · Cells · doi:10.3390/cells10030593 · Cited by 24
Apolipoprotein E ablation decreases synaptic vesicular zinc in the brain
Lee, J., Cho, E., Kim, T.-Y., Kim, D., Palmiter, R. D., Volitakis, I., Kim, J. S., Bush, A. I., & Koh, J. (2010) · BioMetals · doi:10.1007/s10534-010-9354-9 · Cited by 23
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
Lysosomal proteomics reveals mechanisms of neuronal APOE4-associated lysosomal dysfunction
Krogsaeter, E., McKetney, J., Valiente‐Banuet, L., Marquez, A., Willis, A., Cakir, Z., Stevenson, E. J., Jang, G. Μ., Rao, A. T., Li, E., et al. (2025) · Autophagy · doi:10.1080/15548627.2025.2576613 · Cited by 22
Peripheral Pathways to Neurovascular Unit Dysfunction, Cognitive Impairment, and Alzheimer’s Disease
Nelson, A. R. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.858429 · Cited by 24
Blood brain barrier-on-a-chip to model neurological diseases
Reshma, S. C., Megha, K. B., Amir, S., Rukhiya, S., & Mohanan, P. V. (2023) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2023.104174 · Cited by 23
Grimmer, T., Goldhardt, O., Guo, L., Yousefi, B. H., Förster, S., Drzezga, A. E., Sorg, C., Alexopoulos, P., Förstl, H., Kurz, A., et al. (2014) · NeuroImage Clinical · doi:10.1016/j.nicl.2014.01.016 · Cited by 23
Protein structures in Alzheimer's disease: The basis for rationale therapeutic design
Montoliu‐Gaya, L., & Villegas, S. (2015) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2015.10.005 · Cited by 24
Early detection and personalized medicine: Future strategies against Alzheimer's disease
Meco, A. D., & Vassar, R. J. (2020) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2020.10.002 · Cited by 24
Cell type-specific functions of Alzheimer's disease endocytic risk genes
Maninger, J.-K., Nowak, K., Goberdhan, S., O'Donoghue, R., & Connor-Robson, N. (2024) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2022.0378 · Cited by 22
Лю, Ч., Liu, J., Wang, Y., Xu, S.-F., & Yu, L.-M. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-05629-3 · Cited by 22
Yang, L., Chen, Z., Wan, X., Liu, M., Wu, J., Chen, Y., Zhang, G., & Fan, Z. (2021) · International Journal of Neuroscience · doi:10.1080/00207454.2021.1946056 · Cited by 21
Retracted: Advances in the physiological and pathological implications of cholesterol
Cortés, V., Busso, D., Mardones, P., Alberto Maiz, G., Arteaga, A., Nervi, F. O., & Rigotti, A. (2013) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/brv.12025 · Cited by 23
RetractedMontoliu‐Gaya, L., Güell‐Bosch, J., Esquerda-Canals, G., Roda, A. R., Serra-Mir, G., Lope‐Piedrafita, S., Sánchez‐Quesada, J. L., & Villegas, S. (2018) · Biochemical Pharmacology · doi:10.1016/j.bcp.2018.07.012 · Cited by 23
Neuronal cholesterol esterification by ACAT1 in Alzheimer's disease
Chang, T., Chang, C. C. Y., Bryleva, E. Y., Rogers, M. A., & Murphy, S. R. (2010) · IUBMB Life · doi:10.1002/iub.305 · Cited by 21
Dual orexin receptor antagonists as promising therapeutics for Alzheimer’s disease
Ragsdale, S. M., Radovich, J. M., Coiduras, I. I., McCall, W. V., Grant, S. C., Lee, C. S., & Wilber, A. A. (2025) · npj Biological Timing and Sleep · doi:10.1038/s44323-025-00025-5 · Cited by 20
McInerney, M. P., Short, J. L., & Nicolazzo, J. A. (2017) · The AAPS Journal · doi:10.1208/s12248-017-0077-5 · Cited by 20
Vascular endothelial cells: a fundamental approach for brain waste clearance
Wei, H., Jiang, H., Zhou, Y., Xiao, X., Zhou, C., & Ji, X. (2022) · Brain · doi:10.1093/brain/awac495 · Cited by 20
Hua, J., Paco, E. G. D., Linck, N., Maurice, T., Desrumaux, C. M., Manoury, B., Rassendren, F., & Ulmann, L. (2023) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-023-04784-x · Cited by 22
Hu, Y., Meuret, C., Martinez, A., Yassine, H. N., & Nedelkov, D. (2021) · Journal of Lipid Research · doi:10.1194/jlr.ra120000919 · Cited by 18
Haptoglobin Modulates Beta-Amyloid Uptake by U-87 MG Astrocyte Cell Line
Maresca, B., Spagnuolo, M. S., & Cigliano, L. (2015) · Journal of Molecular Neuroscience · doi:10.1007/s12031-014-0465-6 · Cited by 20
Hu, H., Wan, S., Hu, Y., Wang, Q., Li, H., & Zhang, N. (2025) · Annals of Medicine · doi:10.1080/07853890.2024.2445194 · Cited by 20
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
Ramakrishnan, V., Friedrich, C. M., Witt, C. M., Sheehan, R., Pryor, M. M., Atwal, J. K., Wildsmith, K. R., Kudrycki, K., Lee, S., Mazer, N. A., et al. (2022) · CPT Pharmacometrics & Systems Pharmacology · doi:10.1002/psp4.12876 · Cited by 19
When Will Alzheimer's Disease be Cured? A Pharmaceutical Perspective
Townsend, M. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-110020 · Cited by 19
Role of APOE ε4 Allele and Incident Stroke on Cognitive Decline and Mortality
Rajan, K. B., Aggarwal, N. T., Schneider, J. A., Wilson, R. S., Everson‐Rose, S. A., & Evans, D. A. (2016) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0000000000000173 · Cited by 19
Choroid plexus APP regulates adult brain proliferation and animal behavior
Arnaud, K., Moreira, V. O., Vincent, J., Dallérac, G., Dubreuil, C., Dupont, E., Richter, M., Müller, U. C., Rondi-Reig, L., Prochiantz, A., et al. (2021) · Life Science Alliance · doi:10.26508/lsa.202000703 · Cited by 17
Rajpoot, J., Crooks, E. J., Irizarry, B. A., Amundson, A., Nostrand, W. E. V., & Smith, S. O. (2022) · Biochemistry · doi:10.1021/acs.biochem.1c00781 · Cited by 20
Pedrini, S., Doecke, J. D., Hone, E., Wang, P., Thota, R. N., Bush, A. I., Rowe, C. C., Doré, V., Villemagne, V. L., Ames, D. J., et al. (2022) · Journal of Neurochemistry · doi:10.1111/jnc.15681 · Cited by 20
Neustadtl, A. L., Winston, C. N., Parsadanian, M., Main, B. S., Villapol, S., & Burns, M. P. (2017) · Neuroreport · doi:10.1097/wnr.0000000000000811 · Cited by 22
Desikan, R. S., McEvoy, L. K., Holland, D., Thompson, W., Brewer, J. B., Aisen, P. S. S., Andreassen, O. A., Hyman, B. T., Sperling, R. A., Dale, A. M., et al. (2012) · American Journal of Neuroradiology · doi:10.3174/ajnr.a3267 · Cited by 18
Cerebral amyloid angiopathy distribution in older people: A cautionary note
Alakbarzade, V., French, J. M. R., Howlett, D. R., Attems, J., Francis, P. T., Stratton, S., Clark, C. N., Pereira, A. C., & Hainsworth, A. H. (2021) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1002/trc2.12145 · Cited by 20
COVID‐19 and the impact on Alzheimer's disease pathology
Furman, S., Green, K. N., & Lane, T. E. (2023) · Journal of Neurochemistry · doi:10.1111/jnc.15985 · Cited by 18
Marca, V. L., Spagnuolo, M. S., Cigliano, L., Marasco, D., & Abrescia, P. (2014) · Journal of Neurochemistry · doi:10.1111/jnc.12713 · Cited by 18
Bonaterra‐Pastra, A., de Retana, S. F., Rivas-Urbina, A., Puig, N., Benı́tez, S., Pancorbo, O., Rodríguez‐Luna, D., Pujadas, F., Freijo, M. D. M., Tur, S., et al. (2021) · Biomedicines · doi:10.3390/biomedicines9010072 · Cited by 21
Aydin, N., Türkez, H., Tozlu, Ö. Ö., Arslan, M. E., Yavuz, M., Sönmez, E., Özpolat, Ö. F., Cacciatore, I., Stefano, A. D., & Mardinoğlu, A. (2022) · Nanomaterials · doi:10.3390/nano12152690 · Cited by 18
Metadata
- Authors
- Deane, R., Sagare, A., Hamm, K., Parisi, M., Lane, S., Finn, M. B., Holtzman, D. M., & Zlokovic, B. V.
- Affiliations
- University of Rochester Medicine (US)
- Washington University in St. Louis (US)
- Venue
- Journal of Clinical Investigation
- Published
- 2008-12-01
- Volume
- 118
- Issue
- 12
- Pages
- 4002-4013
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC2582453
- OpenAlex
- W2138992210
- Cited by
- 771
- References
- 71
- Citations by year
- 2026: 35 · 2025: 39 · 2024: 51 · 2023: 40 · 2022: 42 · 2021: 48 · 2020: 47 · 2019: 47 · 2018: 35 · 2017: 49 · 2016: 38 · 2015: 51 · 2014: 48 · 2013: 41 · 2012: 52
- FWCI
- 24.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- Funders
- National Institutes of Health (R37 NS34467, NS34467, AG13956, R37 AG13956)
- National Institute on Aging (R37AG023084, R37AG13956, R37AG013956)
- National Institute of Neurological Disorders and Stroke (R37NS034467, R37NS34467)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- APOE isoforms, APOE ε4, Alzheimer's disease, blood-brain barrier, LRP1, VLDLR, APOE2, APOE3, amyloid accumulation
- MeSH terms
- Alzheimer Disease, Animals, Astrocytes, Blood-Brain Barrier, Disease Models, Animal, Humans, Male, Receptors, LDL, Amyloid beta-Peptides, Protein Isoforms, Tumor Suppressor Proteins, Low Density Lipoprotein Receptor-Related Protein-1, Mice, Apolipoprotein E3, Apolipoprotein E4
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
