ApoE-isoform-dependent cellular uptake of amyloid-β is mediated by lipoprotein receptor LR11/SorLA
Abstract
The formation of senile plaques composed of β-amyloid (Aβ) in the brain is likely the initial event in Alzheimer's disease (AD). Possession of the APOE ε4 allele, the strong genetic factor for AD, facilitates the Aβ deposition from the presymptomatic stage of AD in a gene-dosage-dependent manner. However, the precise mechanism by which apoE isoforms differentially induce the AD pathology is largely unknown. LR11/SorLA is a type I membrane protein that functions as the neuronal lipoprotein endocytic receptor of apoE and the sorting receptor of the amyloid precursor protein (APP) to regulate amyloidogenesis. Recently, LR11/SorLA has been reported to be involved in the lysosomal targeting of extracellular amyloid-β (Aβ) through the binding of Aβ to the vacuolar protein sorting 10 (VPS10) protein domain of LR11/SorLA. Here, we attempted to examine the human-apoE-isoform-dependent effect on the cellular uptake of Aβ through the formation of a complex between an apoE isoform and LR11/SorLA. Cell culture experiments using Neuro2a cells revealed that the cellular uptake of secreted apoE3 and apoE4 was enhanced by the overexpression of LR11/SorLA. In contrast, the cellular uptake of apoE2 was not affected by the expression of LR11/SorLA. Co-immunoprecipitation assay revealed that apoE-isoform-dependent differences were observed in the formation of an apoE-LR11 complex (apoE4>apoE3>apoE2). ApoE-isoform-dependent differences in cellular uptake of FAM-labeled Aβ were further investigated…
Integrity signals
Registry
Cites
Statistics
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?
The cleavage of APP to Aβ in BACE-containing endosomes is exacerbated by the APOE E4 genotype.
“APP can be cleaved to Aβ (Fig. 5, magenta) when it is trapped in endosomes that contain β-secretase (BACE)143, a process exacerbated by the APOE E4 genotype144,145.”
From Stress weakens prefrontal networks: molecular insults to higher cognition (2015) · cites this paper as [145]
Cites
Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease
Corder, E. H., Saunders, A. M., Risch, N. J., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Rimmler, J. B., Locke, P. A., Conneally, P. M., Schmader, K. E., et al. (1994) · Nature Genetics · doi:10.1038/ng0694-180 · Cited by 1,920 · see citing works
Lacor, P. N., Buniel, M. C., Furlow, P. W., Sanz Clemente, A., Velasco, P. T., Wood, M., Viola, K. L., & Klein, W. L. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.3501-06.2007 · Cited by 1,188 · see citing works
Amyloid seeds formed by cellular uptake, concentration, and aggregation of the amyloid-beta peptide
Hu, X., Crick, S. L., Bu, G., Frieden, C., Pappu, R. V., & Lee, J.-M. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0911281106 · Cited by 426 · see citing works
Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease
Wahrle, S. E., Jiang, H., Parsadanian, M., Kim, J., Li, A., Knoten, A., Jain, S., Hirsch-Reinshagen, V., Wellington, C. L., Bales, K. R., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci33622 · Cited by 370 · see citing works
Kim, J., Castellano, J. M., Jiang, H., Basak, J. M., Parsadanian, M., Pham, V., Mason, S. M., Paul, S. M., & Holtzman, D. M. (2009) · Neuron · doi:10.1016/j.neuron.2009.11.013 · Cited by 274 · see citing works
TOKUDA, T., CALERO, M., MATSUBARA, E., VIDAL, R., KUMAR, A., PERMANNE, B., ZLOKOVIC, B., SMITH, J. D., LADU, M. J., ROSTAGNO, A., et al. (2000) · Biochemical Journal · doi:10.1042/bj3480359 · Cited by 272 · see citing works
Miyashita, A., Koike, A., Jun, G., Wang, L.-S., Takahashi, S., Matsubara, E., Kawarabayashi, T., Shoji, M., Tomita, N., Arai, H., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0058618 · Cited by 196 · see citing works
Self-citationDodson, S. E., Andersen, O. M., Karmali, V., Fritz, J. J., Cheng, D., Peng, J., Levey, A. I., Willnow, T. E., & Lah, J. J. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.4582-08.2008 · Cited by 141 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Stress weakens prefrontal networks: molecular insults to higher cognition
Arnsten, A. F. T. (2015) · Nature Neuroscience · doi:10.1038/nn.4087 · Cited by 752 · see citing works
Multi-cellular communities are perturbed in the aging human brain and Alzheimer’s disease
Cain, A., Taga, M., McCabe, C., Green, G., Hekselman, I., White, C. C., Lee, D. I., Gaur, P., Rozenblatt-Rosen, O., Zhang, F., et al. (2020) · doi:10.1101/2020.12.22.424084 · Cited by 143 · see citing works
- Authors
- Yajima, R., Tokutake, T., Koyama, A., Kasuga, K., Tezuka, T., Nishizawa, M., & Ikeuchi, T.
- Affiliations
- Brain Research Institute, Niigata University (JP)
- Niigata University (JP)
- Corresponding author
- Ikeuchi, Takeshi
- ORCID
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2015-01
- Volume
- 456
- Issue
- 1
- Pages
- 482-488
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2050638819
- Cited by
- 43
- References
- 8
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 5 · 2023: 9 · 2022: 7 · 2021: 1 · 2020: 5 · 2019: 5 · 2018: 2 · 2017: 1 · 2016: 1 · 2015: 3
- FWCI
- 1.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (20372469, 23591234)
- Ministry of Health, Labour and Welfare
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- amyloid-beta, APOE isoforms, cellular uptake, Alzheimer's disease, APOE ε4, APOE3, APOE2, lipoprotein receptors, N2a cells
- MeSH terms
- Alleles, Animals, Apolipoproteins E, Brain, Cloning, Molecular, Humans, Microscopy, Fluorescence, Oxygen, Receptors, LDL, Amyloid beta-Peptides, DNA, Complementary, Microscopy, Confocal, Coculture Techniques, Protein Isoforms, LDL-Receptor Related Proteins, Membrane Transport Proteins, Cell Line, Tumor, Mice, HEK293 Cells
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
