The DOI matches its Crossref record; 45 of the 47 references it cites were found in a registry or an index.
Amyloid seeds formed by cellular uptake, concentration, and aggregation of the amyloid-beta peptide
Open accessAbstract
One of the neuropathological hallmarks of Alzheimer's disease (AD) is the amyloid plaque, primarily composed of aggregated amyloid-beta (Aβ) peptide. In vitro, Aβ 1–42 , the major alloform of Aβ found in plaques, self-assembles into fibrils at micromolar concentrations and acidic pH. Such conditions do not exist in the extracellular fluid of the brain where the pH is neutral and Aβ concentrations are in the nanomolar range. Here, we show that extracellular soluble Aβ (sAβ) at concentrations as low as 1 nM was taken up by murine cortical neurons and neuroblastoma (SHSY5Y) cells but not by human embryonic kidney (HEK293) cells. Following uptake, Aβ accumulated in Lysotracker-positive acidic vesicles (likely late endosomes or lysosomes) where effective concentrations (>2.5 μM) were greater than two orders of magnitude higher than that in the extracellular fluid (25 nM), as quantified by fluorescence intensity using laser scanning confocal microscopy. Furthermore, SHSY5Y cells incubated with 1 μM Aβ 1–42 for several days demonstrated a time-dependent increase in intracellular high molecular weight (HMW) (>200 kDa) aggregates, which were absent in cells grown in the presence of Aβ 1–40 . Homogenates from these Aβ 1–42 -loaded cells were capable of seeding amyloid fibril growth. These results demonstrate that Aβ can be taken up by certain cells at low physiologically relevant concentrations of extracellular Aβ, and then concentrated into endosomes/lysosomes. At high concentrations, vesicular Aβ aggregates to form HMW species which are capable of seeding amyloid fibril growth. We speculate that extrusion of these aggregates may seed extracellular amyloid plaque formation during AD pathogenesis.
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
“Although amyloid beta plaques are extracellular, mounting evidence suggests that aggregation also begins within neurons, where uptake and subsequent degradation within lysosomes has been dysregulated leading to intraneuronal accumulation leading to aggregation [14–20].”
From The Sigma-2 Receptor/TMEM97, PGRMC1, and LDL Receptor Complex Are Responsible for the Cellular Uptake of Aβ42 and Its Protein Aggregates (2020) · cites this paper as [19]
Experimental — accuracy not yet measuredIn the citing paper
“In contrast to the extracellular space, microglial lysosomes provide a suitable environment to facilitate Aβ aggregation, potentially contributing to the onset of plaque pathology15.”
From Sustained microglial depletion with CSF1R inhibitor impairs parenchymal plaque development in an Alzheimer’s disease model (2019) · cites this paper as [15]
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
Glenner, G. G., & Wong, C. W. (1984) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(84)80190-4 · Cited by 5,404
Walsh, D. M., Klyubin, I., Fadeeva, J. V., Cullen, W. K., Anwyl, R., Wolfe, M. S., Rowan, M. J., & Selkoe, D. J. (2002) · Nature · doi:10.1038/416535a · Cited by 4,291
Triple-Transgenic Model of Alzheimer’s Disease with Plaques and Tangles
Oddo, S., Caccamo, A., Shepherd, J. D., Murphy, M. P., Golde, T. E., Kayed, R., Metherate, R., Mattson, M. P., Akbari, Y., & LaFerla, F. M. (2003) · Neuron · doi:10.1016/s0896-6273(03)00434-3 · Cited by 4,126
Intracellular amyloid-β in Alzheimer's disease
LaFerla, F. M., Green, K. N., & Oddo, S. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2168 · Cited by 1,942
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
Harper, J. D., & Lansbury, P. T. (1997) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.66.1.385 · Cited by 1,652
Synaptic Activity Regulates Interstitial Fluid Amyloid-β Levels In Vivo
Cirrito, J. R., Yamada, K. A., Finn, M. B., Sloviter, R. S., Bales, K. R., May, P. C., Schoepp, D. D., Paul, S. M., Mennerick, S., & Holtzman, D. M. (2005) · Neuron · doi:10.1016/j.neuron.2005.10.028 · Cited by 1,265
Assembly and aggregation properties of synthetic Alzheimer's A4/beta amyloid peptide analogs.
Burdick, D., Soreghan, B., Kwon, M., Kosmoski, J., Knauer, M., Henschen, A., Yates, J., Cotman, C., & Glabe, C. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)48529-8 · Cited by 1,014
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
LRP/Amyloid β-Peptide Interaction Mediates Differential Brain Efflux of Aβ Isoforms
Deane, R., Wu, Z., Sagare, A., Davis, J., Du Yan, S., Hamm, K., Xu, F., Parisi, M., LaRue, B., Hu, H. W., et al. (2004) · Neuron · doi:10.1016/j.neuron.2004.07.017 · Cited by 828
Cited by
Sorted by citations
Items 101–200 of 426
Structure and Dynamics of Amyloid-β Segmental Polymorphisms
Berhanu, W. M., & Hansmann, U. (2012) · PLoS ONE · doi:10.1371/journal.pone.0041479 · Cited by 73
“Experimental studies have shown that the morphology of Ab fibrils is highly sensitive to environmental conditions [10], [13].”
BackgroundD’Angelo, F., Vignaud, H., Martino, J. S. D., Salin, B., Devin, A., Cullin, C., & Marchal, C. (2012) · Disease Models & Mechanisms · doi:10.1242/dmm.010108 · Cited by 80
“Recent publications have confirmed the important role played by intracellular A, whether it is produced through the secretion pathway, by transfection or by uptake from the medium (Echeverria et al., 2004; Hansson Petersen et al., 2008; Hu et al., 2009; Kandimalla et al., 2009; Rebeck et al., 2010).”
Tam, J. H. K., Seah, C., & Pasternak, S. (2014) · Molecular Brain · doi:10.1186/s13041-014-0054-1 · Cited by 83
“seeding [109–111].”
Brännström, K., Öhman, A., Nilsson, L., Pihl, M., Sandblad, L., & Olofsson, A. (2014) · Journal of the American Chemical Society · doi:10.1021/ja503535m · Cited by 74
Vandendriessche, C., Bruggeman, A., Cauwenberghe, C. V., & Vandenbroucke, R. E. (2020) · Cells · doi:10.3390/cells9112485 · Cited by 75
“Moreover, the aggregation of Aβ peptides has been shown to occur in acidic cellular compartments, including late endosomes, inside neurons [42,43].”
BackgroundEstrogen activates matrix metalloproteinases-2 and -9 to increase beta amyloid degradation
Merlo, S., & Sortino, M. A. (2012) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2012.02.005 · Cited by 77
“Moreover, undifferentiated SH-SY5Y cells represent a valid model for the analysis of Aβ processing (Hu et al., 2009; Liang et al., 2010).”
BackgroundPrion-like seeding and nucleation of intracellular amyloid-β
Olsson, T. T., Klementieva, O. L., & Gouras, G. K. (2018) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.01.015 · Cited by 74
Corruption and Spread of Pathogenic Proteins in Neurodegenerative Diseases
Walker, L. C., & LeVine, H. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.r112.399378 · Cited by 75
Dual-functional AIE fluorescent probes for imaging β-amyloid plaques and lipid droplets
Wang, Y., Qiu, Y.-T., Sun, A., Xiong, Y., Tan, H.-Y., Shi, Y., Pan, Y. B., Roy, G., Zhang, L., & Yan, J. (2020) · Analytica Chimica Acta · doi:10.1016/j.aca.2020.07.073 · Cited by 70
From degenerative disease to malignant tumors: Insight to the function of ApoE
Miao, G., Zhuo, D., Han, X. N., Yao, W., Liu, C., Liu, H., Cao, H., Sun, Y., Chen, Z., & Feng, T. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.114127 · Cited by 76
Designed Cell-Penetrating Peptide Inhibitors of Amyloid-beta Aggregation and Cytotoxicity
Henning‐Knechtel, A., Kumar, S., Wallin, C., Król, S. K., Wärmländer, S. K. T. S., Jarvet, J., Esposito, G., Kırmızıaltın, S., Gräslund, A., Hamilton, A. D., et al. (2020) · Cell Reports Physical Science · doi:10.1016/j.xcrp.2020.100014 · Cited by 69
Phospholipase D3 degrades mitochondrial DNA to regulate nucleotide signaling and APP metabolism
Acker, Z. P. V., Perdok, A., Hellemans, R., North, K., Vorsters, I., Cappel, C. C., Dehairs, J., Swinnen, J. V., Sannerud, R., Bretou, M., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-38501-w · Cited by 76
Banerjee, S., Hashemi, M., Zagorski, K., & Lyubchenko, Y. L. (2021) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.0c00688 · Cited by 69
Amyloid and Alzheimer's Disease: Inside and Out
Tam, J. H. K., & Pasternak, S. (2012) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/s0317167100013408 · Cited by 64
Prion-like mechanisms in Alzheimer disease
Walker, L. C. (2018) · Handbook of clinical neurology · doi:10.1016/b978-0-444-63945-5.00016-7 · Cited by 67
“Extracellular, soluble Aβ is taken up by cultured cells and concentrated in the acidic environment of endosomes/lysosomes, where the Aβ assembles into higher molecular weight seeds (Hu et al., 2009).”
BackgroundSivilia, S., Lorenzini, L., Giuliani, A., Gusciglio, M., Fernández, M., Baldassarro, V. A., Mangano, C., Ferraro, L., Pietrini, V., Baroc, M. F., et al. (2013) · BMC Neuroscience · doi:10.1186/1471-2202-14-44 · Cited by 65
Interaction between -Synuclein and Other Proteins in Neurodegenerative Disorders
Jellinger, K. A. (2011) · The Scientific World JOURNAL · doi:10.1100/2011/371893 · Cited by 64
“Like other pathogenic proteins, Aβ can be taken up, modified, and secreted by cells in vitro [108, 156], and it is also present in the CSF [157].”
An Imaging and Systems Modeling Approach to Fibril Breakage Enables Prediction of Amyloid Behavior
Xue, W., & Radford, S. E. (2013) · Biophysical Journal · doi:10.1016/j.bpj.2013.10.034 · Cited by 64
Transcriptional Effects of ApoE4: Relevance to Alzheimer’s Disease
Theendakara, V., Peters-Libeu, C. A., Bredesen, D. E., & Rao, R. V. (2018) · Molecular Neurobiology · doi:10.1007/s12035-017-0757-2 · Cited by 63
Cause and consequence of Aβ – Lipid interactions in Alzheimer disease pathogenesis
Rangachari, V., Dean, D. N., Rana, P., Vaidya, A., & Ghosh, P. (2018) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2018.03.004 · Cited by 61
Moon, M., Hong, H.-S., Nam, D. W., Baik, S. H., Song, H., Kook, S.-Y., Kim, Y. S., Lee, J., & Mook-Jung, I. (2012) · Journal of Alzheimer's Disease · doi:10.3233/jad-2011-111778 · Cited by 60
“Based on our observations and previous reports [7–9, 11], we hypothesized that neurons that accumulate A may die and release A into the extracellular space, where it then becomes a hollow-type plaque and continues to grow through the accumulation of soluble A .”
Self-citationDomert, J., Sackmann, C., Severinsson, E., Agholme, L., Bergström, J. J. E., Ingelsson, M., & Hallbeck, M. (2016) · PLoS ONE · doi:10.1371/journal.pone.0168700 · Cited by 59
Helwig, M., Hoshino, A., Berridge, C., Lee, S., Lorenzen, N., Otzen, D. E., Eriksen, J. L., & Lindberg, I. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.417071 · Cited by 59
“Interestingly, cellular reuptake of A into endosomes and lysosomes has been reported to facilitate its aggregation (37).”
BackgroundGrimm, M. O. W., Zinser, E. G., Grösgen, S., Hundsdörfer, B., Rothhaar, T. L., Burg, V. K., Kaestner, L., Bayer, T. A., Lipp, P., Müller, U., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0034095 · Cited by 59
“Because Ab is secreted and taken up by cells [40,41] and since there are, especially in neural cells, abundant amounts of Ab present intracellularly [42,43,44], binding of Ab to GM3 could in principle take place in any intracellular compartment, especially along the secretory pathway and endosomes, at the plasma membr…”
BackgroundPhosphorylation of serine 349 of p62 in Alzheimer’s disease brain
Tanji, K., Miki, Y., Ozaki, T., Maruyama, A., Yoshida, H., Mimura, J., Matsumiya, T., Mori, F., Imaizumi, T., Itoh, K., et al. (2014) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-2-50 · Cited by 59
“AntiAβ oligomer antibody clearly showed positive signals in cells treated with Aβ42, but not with Aβ40, and we confirmed that only Aβ42 was accumulated in lysosomes using confocal microscopy as previously described [36-38].”
MethodBanerjee, S., Hashemi, M., Lv, Z., Maity, S., Rochet, J., & Lyubchenko, Y. L. (2017) · Scientific Reports · doi:10.1038/srep45592 · Cited by 58
“For example, whereas the critical concentration for the spontaneous aggregation of A β peptide in vitro is in the micromolar range, physiological concentrations of A β are in the low nanomolar range 18,19 .”
Cryptotanshinione Inhibits β-Amyloid Aggregation and Protects Damage from β-Amyloid in SH-SY5Y Cells
Mei, Z., Yan, P., Situ, B., Mou, Y., & Liu, P. (2011) · Neurochemical Research · doi:10.1007/s11064-011-0652-6 · Cited by 57
Smid, S. D., Mååg, J. L. V., & Musgrave, I. (2012) · Food & Function · doi:10.1039/c2fo30075c · Cited by 57
Expression and Processing of Amyloid Precursor Protein in Vascular Endothelium
d’Uscio, L. V., He, T., & Katušić, Z. S. (2016) · Physiology · doi:10.1152/physiol.00021.2016 · Cited by 57
ApoHRP-based assay to measure intracellular regulatory heme
Atamna, H., Brahmbhatt, M., Atamna, W., Shanower, G., & Dhahbi, J. M. (2014) · Metallomics · doi:10.1039/c4mt00246f · Cited by 56
Tau pathogenesis is promoted by Aβ1-42 but not Aβ1-40
Hu, X., Li, X., Zhao, M., Gottesdiener, A., Luo, W., & Paul, S. M. (2014) · Molecular Neurodegeneration · doi:10.1186/1750-1326-9-52 · Cited by 55
“Methods Aβ Preparation: Aβ1–42 and Aβ1–40 Dry peptide (1 mg) was pretreated with neat trifluoroacetic acid (1 mL), distilled under nitrogen, washed with 1,1,1,3,3,3-hexafluoro-2-propanol (1 mL), distilled under nitrogen, then dissolved in DMSO to 10 mM, and stored at −20°C [26].”
MethodSelf-citationAmyloid Oligomer Neurotoxicity, Calcium Dysregulation, and Lipid Rafts
Malchiodi‐Albedi, F., Paradisi, S., Matteucci, A., Frank, C., & Diociaiuti, M. (2011) · International Journal of Alzheimer s Disease · doi:10.4061/2011/906964 · Cited by 55
“The process has also been characterized in vitro, showing that homogenates from SHSY5Y cells, which had uptaken Aβ, were capable of seeding amyloid fibril growth [88].”
BackgroundAntonios, G., Saiepour, N., Bouter, Y., Richard, B. C., Paetau, A., Verkkoniemi-Ahola, A., Lannfelt, L., Ingelsson, M., Kovacs, G. G., Pillot, T., et al. (2013) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-1-56 · Cited by 53
“At high concentrations, vesicular fulllength Aβ aggregates form high molecular weight oligomers which are capable of seeding amyloid fibril growth [49].”
BackgroundA novel function for pro SAAS as an amyloid anti‐aggregant in Alzheimer's disease
Hoshino, A., Helwig, M., Rezaei, S., Berridge, C., Eriksen, J. L., & Lindberg, I. (2013) · Journal of Neurochemistry · doi:10.1111/jnc.12454 · Cited by 52
“While the majority of Ab/proSAAS co-localization clearly occurs extracellularly, the latter possibility is intriguing since it has been shown that Ab1–42 accumulates in acidic vesicles where it becomes concentrated and begins to aggregate (Hu et al. 2009).”
BackgroundImpact of GM1 on Membrane-Mediated Aggregation/Oligomerization of β-Amyloid: Unifying View
Cebecauer, M., Hof, M., & Amaro, M. (2017) · Biophysical Journal · doi:10.1016/j.bpj.2017.03.009 · Cited by 51
Amyloid oligomers as on-pathway precursors or off-pathway competitors of fibrils
Muschol, M., & Hoyer, W. (2023) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2023.1120416 · Cited by 56
“The strong dependence of the protein threshold for oligomer formation on localized amyloid concentrations and solution conditions, in particular pH, match with direct observation that conditions for preferential oligomer formation in vivo involve acidic cellular compartments (Hu et al., 2009; Schützmann et al., 2021).”
BackgroundMeli, G., Lecci, A., Manca, A., Jakovljevic, N. K., Albertini, V., Benussi, L., Ghidoni, R., & Cattaneo, A. (2014) · Nature Communications · doi:10.1038/ncomms4867 · Cited by 51
Current understanding of metal-dependent amyloid-β aggregation and toxicity
Yi, Y., & Lim, M. H. (2022) · RSC Chemical Biology · doi:10.1039/d2cb00208f · Cited by 50
Cellular mechanism of fibril formation from serum amyloid A1 protein
Claus, S., Meinhardt, K., Aumüller, T., Puşcalău-Gîrţu, I., Linder, J., Haupt, C., Walther, P., Syrovets, T., Simmet, T., & Fändrich, M. (2017) · EMBO Reports · doi:10.15252/embr.201643411 · Cited by 48
“…of b 2-microglobulin in dialysis-related amyloidosis [51], the formation of apolipoprotein A-I amyloid deposits in ApoA-I amyloidosis [52] and the deposition of amyloid plaques from A b peptide or prion protein in Alzheimer’s disease or trans-missible spongiform encephalopathy [41,42,46,53,54].”
Pedrioli, G., & Paganetti, P. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.595515 · Cited by 50
Direct interaction of beta-amyloid with Na,K-ATPase as a putative regulator of the enzyme function
Petrushanko, I. Y., Mitkevich, V. A., Anashkina, A. A., Adzhubei, A. A., Burnysheva, K. M., Lakunina, V. A., Kamanina, Y. V., Dergousova, E. A., Lopina, O. D., Ogunshola, O. O., et al. (2016) · Scientific Reports · doi:10.1038/srep27738 · Cited by 49
“We have found that the Na,K-ATPase:Aβ (1-42) complex formation leads to the dose-dependent loss of hydrolytic activity of the enzyme in solution and in neuroblastoma cells SH-SY5Y.”
BackgroundMethodInfluentialMorel, B., Carrasco, M. P., Jurado, S., Marco, C., & Conejero‐Lara, F. (2018) · Physical Chemistry Chemical Physics · doi:10.1039/c8cp02685h · Cited by 50
Yang, X., Chen, Y.-H., Liu, L., Gu, Z., You, Y., Hao, J., Sun, N., & Gao, C. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107357 · Cited by 49
Differential Activation of the ER Stress Factor XBP1 by Oligomeric Assemblies
Castillo‐Carranza, D. L., Zhang, Y., Guerrero‐Munoz, M. J., Kayed, R., Rincón-Limas, D. E., & Fernández-Fúnez, P. (2012) · Neurochemical Research · doi:10.1007/s11064-012-0780-7 · Cited by 51
“Finally, oligomers can be actively transported by endocytic mechanisms, resulting in intracellular accumulation and interaction with the protein quality-control mechanism, including chaperones and the proteasome [19].”
BackgroundJohnson, R. D., Schauerte, J. A., Wisser, K. C., Gafni, A., & Steel, D. G. (2011) · PLoS ONE · doi:10.1371/journal.pone.0023970 · Cited by 48
β-Amyloid Peptide: the Cell Compartment Multi-faceted Interaction in Alzheimer’s Disease
Picone, P., Nuzzo, D., Giacomazza, D., & Carlo, M. D. (2019) · Neurotoxicity Research · doi:10.1007/s12640-019-00116-9 · Cited by 47
Optical Nanosensor for Intracellular and Intracranial Detection of Amyloid-Beta
Antman‐Passig, M., Wong, E., Frost, G. R., Cupo, C., Shah, J., Agustinus, A. S., Chen, Z., Mancinelli, C. D., Kamel, M., Li, T., et al. (2022) · ACS Nano · doi:10.1021/acsnano.2c00054 · Cited by 45
Targeting ApoE4/ApoE receptor LRP1 in Alzheimer's disease
Martiskainen, H., Haapasalo, A., Kurkinen, K. M. A., Pihlajamäki, J., Soininen, H. S., & Hiltunen, M. O. (2013) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2013.789862 · Cited by 49
“Ab42 internalized by LRP1 into neurons was directed to lysosomes for degradation in these studies.”
BackgroundInfluentialDammers, C., Schwarten, M., Buell, A. K., & Willbold, D. (2017) · Chemical Science · doi:10.1039/c6sc04797a · Cited by 45
Pacheco‐Quinto, J., Clausen, D. M., Pérez‐González, R., Peng, H., Meszaros, A., Eckman, C. B., Levy, E., & Eckman, E. A. (2018) · The FASEB Journal · doi:10.1096/fj.201801319r · Cited by 46
Ari, C., Borysov, S. I., Wu, J., Padmanabhan, J., & Potter, H. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.02.006 · Cited by 44
“3B) as has been previously demonstrated (Hu et al., 2009; Saavedra et al., 2007).”
The 37kDa/67kDa Laminin Receptor acts as a receptor for Aβ42 internalization
Dias, B. D. C., Jovanovic, K., Gonsalves, D., Moodley, K., Reusch, U., Knackmuss, S. H. J., Weinberg, M. S., Little, M., & Weiss, S. F. T. (2014) · Scientific Reports · doi:10.1038/srep05556 · Cited by 44
Volloch, V., & Rits‐Volloch, S. (2023) · Journal of Alzheimer s Disease · doi:10.3233/jad-230164 · Cited by 43
Yang, W., Ma, K., Chen, X. L., Shi, L., Bu, G., Hu, X. D., Han, H., Liu, Y., & Qian, Y. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.08.013 · Cited by 44
Self-citationThe multifaceted role of WNT signaling in Alzheimer’s disease onset and age-related progression.
Kostes, W. W., & Brafman, D. A. (2023) · Cells · doi:10.3390/cells12081204 · Cited by 43
“Along similar lines, impairment of Aβ endosomal trafficking to the lysosomes can lead to defective Aβ uptake [31,37,38].”
BackgroundGriffin, E. F., Scopel, S. E., Stephen, C. A., Holzhauer, A. C., Vaji, M. A., Tuckey, R. A., Berkowitz, L. A., Caldwell, K. A., & Caldwell, G. A. (2019) · Disease Models & Mechanisms · doi:10.1242/dmm.037218 · Cited by 48
“…hallmark of AD, but intracellular A β has been shown to be far more toxic (Burdick et al., 1992; Cha et al., 2012; Esbjörner et al., 2014; Hu et al., 2009; Kounnas et al., 1995; Li et al., 2012; Liu et al., 2013b; Naj et al., 2011; Nakagawa et al., 2000; Okoshi et al., 2015; Reinders et…”
Tang, W., Tam, J. H. K., Seah, C., Chiu, J., Tyrer, A. E., Cregan, S. P., Meakin, S. O., & Pasternak, S. (2015) · Molecular Brain · doi:10.1186/s13041-015-0129-7 · Cited by 42
“seeding of insoluble Aβ [4, 76, 77].”
Aβ Seeding as a Tool to Study Cerebral Amyloidosis and Associated Pathology
Friesen, M., & Meyer‐Luehmann, M. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00233 · Cited by 41
“Recent studies suggested the involvement of endosomes/lysosomes or intracellular assemblies of Aβ to be crucial factors (Hu et al., 2009; Marzesco et al., 2016).”
BackgroundSinha, M. S., Bhowmick, P., Banerjee, A., & Chakrabarti, S. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.09.036 · Cited by 45
ApoE-isoform-dependent cellular uptake of amyloid-β is mediated by lipoprotein receptor LR11/SorLA
Yajima, R., Tokutake, T., Koyama, A., Kasuga, K., Tezuka, T., Nishizawa, M., & Ikeuchi, T. (2015) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2014.11.111 · Cited by 43
Autophagy-lysosomal pathway impairment and cathepsin dysregulation in Alzheimer’s disease
Mançano, A. S. F., Pina, J. G., Froes, B. R., & Sciani, J. M. (2024) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2024.1490275 · Cited by 51
Conicella, A. E., & Fawzi, N. L. (2014) · Biochemistry · doi:10.1021/bi500131a · Cited by 41
Selective localization of Alzheimer's amyloid beta in membrane lateral compartments
Morita, M., Hamada, T., Tendo, Y., Hata, T., Vestergaard, M. C. M., & Takagi, M. (2012) · Soft Matter · doi:10.1039/c2sm07185a · Cited by 41
Dual-functional red-emitting fluorescent probes for imaging beta-amyloid plaques and viscosity
Tan, H.-Y., Zhou, K., Yan, J., Sun, H., Pistolozzi, M., Cui, M., & Zhang, L. (2019) · Sensors and Actuators B Chemical · doi:10.1016/j.snb.2019.126903 · Cited by 41
Amyloid β oligomers inhibit growth of human cancer cells
Pavliukevičienė, B., Zentelytė, A., Jankunec, M., Valiulienė, G., Talaikis, M., Navakauskienė, R., Niaura, G., & Valinčius, G. (2019) · PLoS ONE · doi:10.1371/journal.pone.0221563 · Cited by 42
Cai, J., Dao, P., Chen, H., Yan, L., Li, Y. L., Zhang, W., Li, L., Du, Z., Dong, C., & Meunier, B. (2019) · Dyes and Pigments · doi:10.1016/j.dyepig.2019.107968 · Cited by 43
Amyloid β Fibril Elongation by Monomers Involves Disorder at the Tip
Bacci, M., Vymětal, J., Mihajlovic, M., Caflisch, A., & Vitalis, A. (2017) · Journal of Chemical Theory and Computation · doi:10.1021/acs.jctc.7b00662 · Cited by 39
Copper mediated amyloid-β binding to Transthyretin
Ciccone, L., Fruchart‐Gaillard, C., Mourier, G., Savko, M., Nencetti, S., Orlandini, E., Servent, D., Stura, E. A., & Shepard, W. (2018) · Scientific Reports · doi:10.1038/s41598-018-31808-5 · Cited by 38
Thellung, S., Corsaro, A., Villa, V., Simi, A., Vella, S., Pagano, A., & Florio, T. (2011) · Cell Death and Disease · doi:10.1038/cddis.2011.21 · Cited by 37
“Impairment of lysosomal activity also contributes to Alzheimer disease pathogenesis(29) with Ab peptides functioning as seeds for amyloid formation in acidic vesicles.(22) In TSE, PrP uptake in neurons occurs in the early phases of disease, allowing the formation of new PrP molecule and their diffusion into surroundin…”
BackgroundInvestigating Interventions in Alzheimer's Disease with Computer Simulation Models
Proctor, C. J., Boche, D., Gray, D. A., & Nicoll, J. A. R. (2013) · PLoS ONE · doi:10.1371/journal.pone.0073631 · Cited by 38
“Therefore we parameterised our model using data from a cellular system [38]and carried out all the simulations over a 12 day period.”
Candreva, J., Chau, E., Rice, M. E., & Kim, J. R. (2019) · Biochemistry · doi:10.1021/acs.biochem.9b00655 · Cited by 39
The dense-core plaques of Alzheimer’s disease are granulomas
Lemke, G., & Huang, Y. (2022) · Journal of Experimental Medicine · doi:10.1084/jem.20212477 · Cited by 37
“Neither of these conditions is present in the extracellular space of the brain, but both are present in the confined acidic environment of lysosomes (Fu et al., 2012; Hu et al., 2009).”
BackgroundMajor Reaction Coordinates Linking Transient Amyloid-β Oligomers to Fibrils Measured at Atomic Level
Chandra, B., Bhowmik, D., Maity, B. K., Mote, K. R., Dhara, D., Venkatramani, R., Maiti, S., & Madhu, P. K. (2017) · Biophysical Journal · doi:10.1016/j.bpj.2017.06.068 · Cited by 37
Szigeti, K., Ihnatovych, I., Birkaya, B. G., Chen, Z., Ouf, A., Indurthi, D. C., Bard, J., Kann, J., Adams, A., Chaves, L. D., et al. (2020) · EBioMedicine · doi:10.1016/j.ebiom.2020.102892 · Cited by 38
“Amyloid beta uptake was performed using fluorescently labelled Ab1 42 as described previously [22].”
MethodEvidence for aggregation-independent, PrP C -mediated Aβ cellular internalization
Foley, A. R., Roseman, G. P., Chan, K., Smart, A., Finn, T. S., Yang, K., Lokey, R. S., Millhauser, G. L., & Raskatov, J. A. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2009238117 · Cited by 38
“An increase in intracellular Aβ can create local gradients of particularly high concentrations of Aβ which may favor intracellular Aβ aggregation, ultimately leading to increased pathogenicity and extracellular release of Aβ aggregates which can further act as a seed for fibril growth (10, 11).”
BackgroundInfluentialThe Butter Flavorant, Diacetyl, Exacerbates β-Amyloid Cytotoxicity
More, S. S., Vartak, A. P., & Vince, R. (2012) · Chemical Research in Toxicology · doi:10.1021/tx3001016 · Cited by 36
Two-Step Amyloid Aggregation: Sequential Lag Phase Intermediates
Castello, F., Paredes, J. M., Ruedas-Rama, M. J., Martı́n, M., Roldán, M., Casares, S., & Orte, Á. (2017) · Scientific Reports · doi:10.1038/srep40065 · Cited by 35
Free Cholesterol Accelerates Aβ Self-Assembly on Membranes at Physiological Concentration
Hashemi, M., Banerjee, S., & Lyubchenko, Y. L. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23052803 · Cited by 35
“However, in the majority of in vitro studies, the Aβ concentrations used are several orders of magnitude higher than the physiologically relevant concentrations [5,6]; no aggregation is observed at the physiological low nanomolar concentration of Aβ.”
BackgroundYuyama, K., & Yanagisawa, K. (2010) · Neuroscience Letters · doi:10.1016/j.neulet.2010.06.080 · Cited by 35
Yeung, P. S.-W., & Axelsen, P. H. (2012) · Journal of the American Chemical Society · doi:10.1021/ja3004478 · Cited by 35
Huang, L., Liu, X., Cheng, B., & Huang, K. (2015) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2015.01.007 · Cited by 34
Takamura, A., Okamoto, Y., Kawarabayashi, T., Yokoseki, T., Shibata, M. S., Mouri, A., Nabeshima, T., Sun, H., Abe, K., Urisu, T., et al. (2011) · Molecular Neurodegeneration · doi:10.1186/1750-1326-6-20 · Cited by 34
“These results place both extracellular [22,32] and intraneuronal AbOs [33,34] centrally within the mechanisms mediating AbOinduced neuronal dysfunction leading to memory loss [26,27].”
iPSC model of CHRFAM7A effect on α7 nicotinic acetylcholine receptor function in the human context
Ihnatovych, I., Nayak, T. K., Ouf, A., Süle, N., Birkaya, B. G., Chaves, L. D., Auerbach, A. L., & Szigeti, K. (2019) · Translational Psychiatry · doi:10.1038/s41398-019-0375-z · Cited by 34
Decock, M., Stanga, S., Octave, J., Dewachter, I., Smith, S. O., Constantinescu, S. N., & Kienlen‐Campard, P. (2016) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2016.00107 · Cited by 35
“Previous studies have shown that Aβ concentrated by more than two orders of magnitude can reach micromolar concentrations in acidic vesicular compartments (Hu et al., 2009).”
BackgroundPreman, 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
“A β , when endocytosed, becomes concentrated in the acidic endosomal compartments, which promotes amyloid fi bril formation and then secretion (Chung et al, 1999; Hu et al, 2009; Knauer et al, 1992).”
Griffin, E. F., Yan, X., Caldwell, K. A., & Caldwell, G. A. (2018) · Human Molecular Genetics · doi:10.1093/hmg/ddy308 · Cited by 34
Effect of acidic pH on the stability of α‐synuclein dimers
Lv, Z., Krasnoslobodtsev, A. V., Zhang, Y., Ysselstein, D., Rochet, J., Blanchard, S. C., & Lyubchenko, Y. L. (2016) · Biopolymers · doi:10.1002/bip.22874 · Cited by 33
Jose, J. C., Chatterjee, P., & Sengupta, N. (2014) · PLoS ONE · doi:10.1371/journal.pone.0106883 · Cited by 32
“intra- or extra-cellular regions of the human brain are associated with multiple neurodegenerative diseases (ND) [1–6].”
BackgroundGwon, Y., Kam, T., Kim, S.-H., Song, S., Park, H., Lim, B., Lee, H., Lee, W., Jo, D., & Jung, Y. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.1996-17.2018 · Cited by 33
“…of intraneuronal A is considered small, several studies suggested that the formation of amyloid seed, which leads to severe neuronal toxicity, is markedly accelerated by the locally concentrated A in the acidic organelles along with endo-lysosomal track (Hu et al., 2009; Poduslo et al., 2012).”
BackgroundAβ seeds and prions: How close the fit?
Rasmussen, J., Jucker, M., & Walker, L. C. (2017) · Prion · doi:10.1080/19336896.2017.1334029 · Cited by 33
“2012 [67] Hu X, Crick SL, Bu G, Frieden C, Pappu RV, Lee JM.”
BackgroundBeal, D. M., Tournus, M., Marchante, R., Purton, T. J., Smith, D. P., Tuite, M. F., Doumic, M., & Xue, W.-F. (2020) · iScience · doi:10.1016/j.isci.2020.101512 · Cited by 29
Ihnatovych, I., Birkaya, B. G., Notari, E., & Szigeti, K. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21249668 · Cited by 31
“Fluor-488- and Fluor-555-labeled Aβ1–42 (AnaSpec, Fremont, CA, USA) were reconstituted and the species was confirmed using Beer’s Law (extinction coefficient = absorbance/concentration/path length), as described previously [20,52].”
MethodChirality Dependence of Amyloid β Cellular Uptake and a New Mechanistic Perspective
Dutta, S., Finn, T. S., Kuhn, A. J., Abrams, B. S., & Raskatov, J. A. (2018) · ChemBioChem · doi:10.1002/cbic.201800708 · Cited by 31
CLT1 targets angiogenic endothelium through CLIC1 and fibronectin
Knowles, L. M., Malik, G., Hood, B. L., Conrads, T. P., & Pilch, J. (2011) · Angiogenesis · doi:10.1007/s10456-011-9247-8 · Cited by 29
Glucose directs amyloid-beta into membrane-active oligomers
Kedia, N., Almisry, M., & Bieschke, J. (2017) · Physical Chemistry Chemical Physics · doi:10.1039/c7cp02849k · Cited by 28
AβPeptide Originated from Platelets Promises New Strategy in Anti-Alzheimer’s Drug Development
Inyushin, M. Y., Sanabria, P., Rojas, L. V., Kucheryavykh, Y. V., & Kucheryavykh, L. Y. (2017) · BioMed Research International · doi:10.1155/2017/3948360 · Cited by 30
“The process of aggregation and amyloid fibril growth may be facilitated by seeding with preformed β-sheet amyloid resulting from cellular uptake, concentration, and aggregation of Aβ within endosomes/ exosomes [13].”
BackgroundLi, M., Zhao, A., Ren, J., & Qu, X. (2017) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.6b00436 · Cited by 28
Whiten, D. R., Brownjohn, P. W., Moore, S., De, S., Strano, A., Zuo, Y., Haneklaus, M., Klenerman, D., & Livesey, F. J. (2020) · Brain Communications · doi:10.1093/braincomms/fcaa146 · Cited by 28
“Due to the high concentration of peptide required for oligomerization, it is presumed that Ab aggregates in vivo are formed intracellularly (Hu et al., 2009; Friedrich et al., 2010).”
Backgroundα-synuclein-assisted oligomerization of β-amyloid (1–42)
Chau, E., & Kim, J. R. (2022) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2022.109120 · Cited by 30
Yang, W., Ma, K., Qian, Y., Zhang, J.-S., Feng, G.-F., Shi, L., Zhang, Z., & Liu, Z. (2015) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2015.04.013 · Cited by 29
Metadata
- Authors
- Hu, X., Crick, S. L., Bu, G., Frieden, C., Pappu, R. V., & Lee, J.-M.
- Affiliations
- Washington University in St. Louis (US)
- Department of Biomedical Engineering and Center for Computational Biology, and
- Department of Pediatrics, Cell Biology and Physiology, and
- Hope Center for Neurological Disorders (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2009-12
- Volume
- 106
- Issue
- 48
- Pages
- 20324-20329
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2787156
- OpenAlex
- W1968721593
- Cited by
- 426
- References
- 47
- Citations by year
- 2026: 16 · 2025: 25 · 2024: 22 · 2023: 36 · 2022: 30 · 2021: 20 · 2020: 22 · 2019: 26 · 2018: 28 · 2017: 36 · 2016: 24 · 2015: 17 · 2014: 30 · 2013: 23 · 2012: 31
- FWCI
- 15.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
- Funders
- Hope Center for Neurological Disorders
- National Institutes of Health
- National Institute on Aging (P01AG030128, R01AG027924)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK13332, R01DK013332)
- National Institute of Neurological Disorders and Stroke (P01 NS32636, R01NS48283, R01 NS67905, R01NS067905, R01NS056114, R01NS048283, P01NS032636)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- amyloid-beta, amyloid-beta 42, Aβ40, Alzheimer's disease, amyloid plaques, lysosomes, late endosomes, cellular uptake, neuroblastoma cells, cortical neurons, amyloid plaque formation
- MeSH terms
- Alzheimer Disease, Animals, Fluorescence, Humans, Neurons, Thiazoles, Immunoblotting, Amyloid beta-Peptides, Microscopy, Confocal, Cytoplasmic Vesicles, Cell Line, Tumor, Mice, Benzothiazoles, Plaque, Amyloid
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
