The DOI matches its Crossref record; 58 of the 59 references it cites were found in a registry or an index.
β-Amyloid Accumulation Impairs Multivesicular Body Sorting by Inhibiting the Ubiquitin-Proteasome System
Open accessAbstract
Increasing evidence links intraneuronal β-amyloid (Aβ 42 ) accumulation with the pathogenesis of Alzheimer’s disease (AD). In Aβ precursor protein (APP) mutant transgenic mice and in human AD brain, progressive intraneuronal accumulation of Aβ 42 occurs especially in multivesicular bodies (MVBs). We hypothesized that this impairs the MVB sorting pathway. We used the trafficking of the epidermal growth factor receptor (EGFR) and TrkB receptor to investigate the MVB sorting pathway in cultured neurons. We report that, during EGF stimulation, APP mutant neurons demonstrated impaired inactivation, degradation, and ubiquitination of EGFR. EGFR degradation is dependent on translocation from MVB outer to inner membranes, which is regulated by the ubiquitin-proteasome system (UPS). We provide evidence that Aβ accumulation in APP mutant neurons inhibits the activities of the proteasome and deubiquitinating enzymes. These data suggest a mechanism whereby Aβ accumulation in neurons impairs the MVB sorting pathway via the UPS in 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 cited source doesn’t support the claim as written.
In the citing paper
“In this model, Ab accumulates along the endosomal/lysomal pathway that leads to dysfunction of multivesicular bodies, causing impairment of the ubiquitin-proteasome system, 9 which also controls the fate of NMDARs undergoing endocytic vesicular trafficking.50”
From Blocking the Interaction between Apolipoprotein E and Aβ Reduces Intraneuronal Accumulation of Aβ and Inhibits Synaptic Degeneration (2013) · cites this paper as [9]
Checked by a reasoning model — may be wrong.
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
“These cultures are characterized by progressive buildup of intraneuronal Ab, which is derived from endogenous Ab escaping exocytosis after cleavage of the APP SW mutant.9,49”
From Blocking the Interaction between Apolipoprotein E and Aβ Reduces Intraneuronal Accumulation of Aβ and Inhibits Synaptic Degeneration (2013) · cites this paper as [9]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“A number of studies have associated intraneuronal Ab buildup with hyperphosphorylation of tau protein, 8 disturbed protein trafficking and sorting, 9 reduced expression of synaptic proteins, 10 and mitochondrial dysfunction.11,12”
From Blocking the Interaction between Apolipoprotein E and Aβ Reduces Intraneuronal Accumulation of Aβ and Inhibits Synaptic Degeneration (2013) · cites this paper as [9]
In the citing paper
“In one study, Aβ-induced abnormalities in MVB endocytic sorting were demonstrated in APP mutant neurons, which appeared to be due to impairment of the ubiquitin proteasome system (UPS; [2]).”
From Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease (2010) · cites this paper as [2]
In the citing paper
“The study went on to provide evidence that abnormalities in MVB sorting were due to Aβ-dependent alterations in the ubiquitin-proteasome system (UPS).”
From Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease (2010) · cites this paper as [2]
In the citing paper
“Using the well established endocytosis of the epidermal growth factor receptor (EGFR), this study demonstrated that specifically the MVB sorting pathway, and not internalization or the recycling pathway, was altered in Aβ accumulating neurons.”
From Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease (2010) · cites this paper as [2]
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
Correlative Memory Deficits, Aβ Elevation, and Amyloid Plaques in Transgenic Mice
Hsiao, K., Chapman, P., Nilsen, S., Eckman, C., Harigaya, Y., Younkin, S., Yang, F., & Cole, G. (1996) · Science · doi:10.1126/science.274.5284.99 · Cited by 4,210
Vassar, R., Bennett, B. D., Babu-Khan, S., Kahn, S., Mendiaz, E. A., Denis, P., Teplow, D. B., Ross, S., Amarante, P., Loeloff, R., et al. (1999) · Science · doi:10.1126/science.286.5440.735 · Cited by 3,876
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
Self-citationMukherjee, S., Ghosh, R. K., & Maxfield, F. R. (1997) · Physiological Reviews · doi:10.1152/physrev.1997.77.3.759 · Cited by 1,299
Receptor downregulation and multivesicular-body sorting
Katzmann, D. J., Odorizzi, G., & Emr, S. D. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm973 · Cited by 1,201
Intraneuronal Aβ42 Accumulation in Human Brain
Gouras, G. K., Tsai, J., Naslund, J., Vincent, B., Edgar, M., Checler, F., Greenfield, J. P., Haroutunian, V., Buxbaum, J. D., Xu, H., et al. (2000) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64700-1 · Cited by 991
Self-citationActivity level controls postsynaptic composition and signaling via the ubiquitin-proteasome system
Ehlers, M. D. (2003) · Nature Neuroscience · doi:10.1038/nn1013 · Cited by 977
The Rab5 effector EEA1 is a core component of endosome docking
Christoforidis, S., McBride, H. M., Burgoyne, R. D., & Zerial, M. (1999) · Nature · doi:10.1038/17618 · Cited by 854
Impaired Proteasome Function in Alzheimer's Disease
Keller, J. N., Hanni, K. B., & Markesbery, W. R. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0750436.x · Cited by 848
Evidence that production and release of amyloid beta-protein involves the endocytic pathway
Koo, E. H., & Squazzo, S. L. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)32449-3 · Cited by 829
Flagged first, then by citations
1 of the 59 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- (2005), Methods Mol Biol, 301, 207
Cited by
Sorted by citations
Items 301–316 of 316
Zampar, S. (2021) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-9004
Exploring the role of protein quality control in aging and age-associated neurodegenerative diseases
Gogia, N., Olmos, V., Haidery, F., Luttik, K. P., Tejwani, L., & Lim, J. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-90235-9.00012-4
Morozov, А. V., Burov, A. V., Funikov, S. Y., Teterina, E. V., Astakhova, T. M., Erokhov, P. A., Ustyugov, A. A., & Карпов, В. Л. (2023) · Molecular Biology · doi:10.31857/s0026898423050142
Insights into Proteostasis System in Ageing and Neurodegenerative Disorders
Mishra, Y., Kumar, R., & Netam, R. K. (2025) · Springer eBooks · doi:10.1007/978-981-96-6202-9_9
Yadav, S. K., Maurya, M. K., Tyagi, C., Rai, R., Bhat, B., & Das, M. (2025) · Springer eBooks · doi:10.1007/978-981-96-6202-9_4
Botté, A., Lainé, J., Xicota, L., Heiligenstein, X., Fontaine, G., Kasri, A., Rivals, I., Goh, P. A., Faklaris, O., Cossec, J., et al. (2020) · Figshare · doi:10.6084/m9.figshare.12560492
Botté, A., Lainé, J., Xicota, L., Heiligenstein, X., Fontaine, G., Kasri, A., Rivals, I., Goh, P. A., Faklaris, O., Cossec, J., et al. (2020) · Figshare · doi:10.6084/m9.figshare.12560498
Konings, S. C., Nyberg, E., Martinsson, I., Thakore, R., Gouras, G. K., & Klementieva, O. L. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.10.697647
Self-citationThe Role of Presynaptic Cytomatrix Protein Bassoon (BSN) in Tau Pathology and Propagation
Oo, W. J., Sia, W. T., Lee, J. Y., Chen, C. H., Chang, W., & Chye, S. M. (2026) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/0118715273400895251129055504
Rôle des ADAM dans le processus physiopathologique de la maladie d'Alzheimer
Laumet, G. O. (2010) · theses.fr (ABES) · doi:10.70675/94126786zf990z488ezb471z5f1d5686766c
Implication du fragment C99 dans l’avènement des phénotypes pathologiques de la maladie d’Alzheimer
Bourgeois, A. (2019) · theses.fr (ABES) · doi:10.70675/bb8ccf34zec6cz4bb6z82b4z3030b9cb28f7
Castelot, R. (2024) · theses.fr (ABES) · doi:10.70675/c2a7ce1ez8caaz4593zbb3azae8add8055b5
From Amyloid Exposure to Genetic Causality: Converging hiPSC-Based Models of Alzheimer’s Disease
Colasuonno, F., Valenza, A., Rossin, F., & Moreno, S. (2026) · Cells · doi:10.3390/cells15191793
Metadata
- Authors
- Almeida, C. G., Takahashi, R. H., & Gouras, G. K.
- Affiliations
- Cornell University (US)
- Corresponding author
- Gouras, Gunnar K.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2006-04-19
- Volume
- 26
- Issue
- 16
- Pages
- 4277-4288
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6673997
- OpenAlex
- W2168538246
- Cited by
- 316
- References
- 59
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 11 · 2023: 26 · 2022: 18 · 2021: 12 · 2020: 17 · 2019: 20 · 2018: 14 · 2017: 15 · 2016: 14 · 2015: 15 · 2014: 10 · 2013: 20 · 2012: 18
- FWCI
- 11.52
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Alzheimer's Association
- American Health Assistance Foundation
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (R01NS045677, NS 045677)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- amyloid-beta deposition, multivesicular bodies, ubiquitin-proteasome system, Alzheimer's disease, epidermal growth factor receptor, TrkB receptor, receptor degradation, ubiquitination, deubiquitinase, proteasome inhibition
- MeSH terms
- Animals, Cells, Cultured, Epidermal Growth Factor, Hippocampus, Humans, Male, Mice, Transgenic, Synaptic Vesicles, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Rats, Sprague-Dawley, Ubiquitin, Proteasome Endopeptidase Complex, Mice, Rats, Proteasome Inhibitors, ErbB Receptors
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
