Cited by 624Alzheimer's disease research and treatmentsProtease and Inhibitor MechanismsDementia and Cognitive Impairment Research

The DOI matches its Crossref record; 55 of the 56 references it cites were found in a registry or an index, and 1 are not checked yet.

ADAM10 is the physiologically relevant, constitutive α‐secretase of the amyloid precursor protein in primary neurons

Open access

Kuhn, Peer‐Hendrik, Wang, Huanhuan, Dislich, Bastian, Colombo, Alessio, Zeitschel, Ulrike, Ellwart, Joachim W, Kremmer, Elisabeth, Roßner, Steffen, Lichtenthaler, Stefan F·2010·The EMBO Journal

DOI 10.1038/emboj.2010.167PMC PMC2944055

Open this paper in CoChat — free account Open PDF

Abstract

The amyloid precursor protein (APP) undergoes constitutive shedding by a protease activity called alpha-secretase. This is considered an important mechanism preventing the generation of the Alzheimer's disease amyloid-beta peptide (Abeta). alpha-Secretase appears to be a metalloprotease of the ADAM family, but its identity remains to be established. Using a novel alpha-secretase-cleavage site-specific antibody, we found that RNAi-mediated knockdown of ADAM10, but surprisingly not of ADAM9 or 17, completely suppressed APP alpha-secretase cleavage in different cell lines and in primary murine neurons. Other proteases were not able to compensate for this loss of alpha-cleavage. This finding was further confirmed by mass-spectrometric detection of APP-cleavage fragments. Surprisingly, in different cell lines, the reduction of alpha-secretase cleavage was not paralleled by a corresponding increase in the Abeta-generating beta-secretase cleavage, revealing that both proteases do not always compete for APP as a substrate. Instead, our data suggest a novel pathway for APP processing, in which ADAM10 can partially compete with gamma-secretase for the cleavage of a C-terminal APP fragment generated by beta-secretase. We conclude that ADAM10 is the physiologically relevant, constitutive alpha-secretase of APP.

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

Crossref · 10.1038/emboj.2010.167

Cites

55 of 56 references verified0 citation errors · 0 not checkable

Statistics

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?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

1 retracted

RETRACTED ARTICLE: APP binds DR6 to trigger axon pruning and neuron death via distinct caspases
Nikolaev, A., McLaughlin, T., O’Leary, D. D. M., & Tessier-Lavigne, M. (2009) · Nature · doi:10.1038/nature07767 · Cited by 992
Retracted
β-Secretase Cleavage of Alzheimer's Amyloid Precursor Protein by the Transmembrane Aspartic Protease BACE
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
Expression profiling reveals off-target gene regulation by RNAi
Jackson, A. L., Bartz, S. R., Schelter, J., Kobayashi, S. V., Burchard, J., Mao, M., Li, B., Cavet, G., & Linsley, P. S. (2003) · Nature Biotechnology · doi:10.1038/nbt831 · Cited by 2,370
Cleavage of Amyloid β Peptide During Constitutive Processing of Its Precursor
Esch, F. S., Keim, P. S., Beattie, E. C., Blacher, R. W., Culwell, A. R., Oltersdorf, T., McClure, D., & Ward, P. J. (1990) · Science · doi:10.1126/science.2111583 · Cited by 1,403
Distinct roles for ADAM10 and ADAM17 in ectodomain shedding of six EGFR ligands
Şahin, U., Weskamp, G., Kelly, K., Zhou, H., Higashiyama, S., Peschon, J. J., Hartmann, D., Säftig, P., & Blobel, C. (2004) · The Journal of Cell Biology · doi:10.1083/jcb.200307137 · Cited by 1,013
Constitutive and regulated α-secretase cleavage of Alzheimer’s amyloid precursor protein by a disintegrin metalloprotease
Lammich, S., Kojro, E., Postina, R., Gilbert, S., Pfeiffer, R., Jasionowski, M., Haass, C., & Fahrenholz, F. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.7.3922 · Cited by 975
Evidence That Tumor Necrosis Factor α Converting Enzyme Is Involved in Regulated α-Secretase Cleavage of the Alzheimer Amyloid Protein Precursor
Buxbaum, J. D., Liu, K.-N., Luo, Y., Slack, J. L., Stocking, K. L., Peschon, J. J., Johnson, R. S., Castner, B. J., Cerretti, D. P., & Black, R. A. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.43.27765 · Cited by 952
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
Alzheimer's Disease: Molecular Understanding Predicts Amyloid-Based Therapeutics
Selkoe, D. J., & Schenk, D. (2003) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.43.100901.140248 · Cited by 829
Beta-amyloid precursor protein cleavage by a membrane-bound protease.
Sisodia, S. S. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.13.6075 · Cited by 738

Show all 55 references

Sorted by citations

Items 301–400 of 624

Regulation of the alternative β-secretase meprin β by ADAM-mediated shedding
Scharfenberg, F., Armbrust, F., Marengo, L., Pietrzik, C., & Becker-Pauly, C. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03179-1 · Cited by 29
Methyl-CpG Binding Protein 2 in Alzheimer Dementia
Kim, B., Choi, Y., Kim, H.-S., & Im, H. (2019) · International Neurourology Journal · doi:10.5213/inj.1938196.098 · Cited by 26
“The γ- and β-secretases sequentially cleave APP to produce amyloid-β.”
BackgroundInfluential
Crystal structure of the Tspan15 LEL domain reveals a conserved ADAM10 binding site
Lipper, C. H., Gabriel, K.-H., Seegar, T. C. M., Dürr, K. L., Tomlinson, M. G., & Blacklow, S. C. (2021) · Structure · doi:10.1016/j.str.2021.10.007 · Cited by 26
Tetraspanins as Potential Modulators of Glutamatergic Synaptic Function
Becic, A., Leifeld, J., Shaukat, J., & Hollmann, M. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2021.801882 · Cited by 28
“…scissors” and is responsible for cleaving the extracellular portion of dozens of transmembrane proteins including amyloid precursor protein (APP), notch, and cadherin (Hartmann et al., 2002; Reiss et al., 2005; Kuhn et al., 2010; Dornier et al., 2012; Groot et al., 2014; Seipold and Saftig, 2016).”
Background
Epidermal ADAM17 Is Dispensable for Notch Activation
Groot, A. J., Cobzaru, C., Weber, S., Säftig, P., Blobel, C., Kopan, R., Vooijs, M., & Franzke, C.-W. (2013) · Journal of Investigative Dermatology · doi:10.1038/jid.2013.162 · Cited by 26
“ADAM17 is the principal sheddase of TNF-α and the majority of the EGFR-ligands (Blobel, 2005; Peschon et al. , 1998), whereas ADAM10 is required for Notch and amyloid precursor protein (APP) shedding (Kuhn et al. , 2010; van Tetering et al. , 2009).”
α-Secretase nonsense mutation (ADAM10 Tyr167*) in familial Alzheimer’s disease
Agüero, P., Sainz, M. J., García‐Ayllón, M., Sáez‐Valero, J., Téllez, R., Guerrero, R., Pérez‐Pérez, J., Jiménez‐Escrig, A., & Gómez‐Tortosa, E. (2020) · Alzheimer s Research & Therapy · doi:10.1186/s13195-020-00708-0 · Cited by 25
Genetic association between ADAM10 gene polymorphism and Alzheimer's disease in a Northern Han Chinese population
Song, J., Yu, J., Liu, M., Yan, C., & Tan, L. (2011) · Brain Research · doi:10.1016/j.brainres.2011.09.008 · Cited by 25
A-Disintegrin and Metalloprotease (ADAM) 10 and 17 promote self-renewal of brain tumor sphere forming cells
Bulstrode, H. J. C. J., Jones, L. M., Siney, E. J., et al. (2012) · Cancer Letters · doi:10.1016/j.canlet.2012.07.022 · Cited by 25
Live-cell monitoring of protein localization to membrane rafts using protein-fragment complementation
Merezhko, M., Pakarinen, E., Uronen, R., & Huttunen, H. J. (2020) · Bioscience Reports · doi:10.1042/bsr20191290 · Cited by 24
UsingDrosophilaModels of Amyloid Toxicity to Study Autophagy in the Pathogenesis of Alzheimer’s Disease
O’Keefe, L. V., & Denton, D. (2018) · BioMed Research International · doi:10.1155/2018/5195416 · Cited by 25
Signaling Functions of Intramembrane Aspartyl-Proteases
Papadopoulou, A. A., & Fluhrer, R. (2020) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.591787 · Cited by 23
The Amyloid Cascade Hypothesis 2.0 for Alzheimer’s Disease and Aging-Associated Cognitive Decline: From Molecular Basis to Effective Therapy
Volloch, V., & Rits‐Volloch, S. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241512246 · Cited by 29
Differential transgene expression patterns in Alzheimer mouse models revealed by novel human amyloid precursor protein‐specific antibodies
Höfling, C., Morawski, M., Zeitschel, U., Zanier, E. R., Moschke, K., Serdaroglu, A., Canneva, F., von Hörsten, S., Simoni, M. G. D., Forloni, G., et al. (2016) · Aging Cell · doi:10.1111/acel.12508 · Cited by 28
“1-VSVG into HEK293T cells as previously described (Kuhn et al., 2010).”
MethodSelf-citation
Considerations on inhibition approaches for proinflammatory functions of ADAM proteases
Yildiz, D., & Ludwig, A. (2016) · Platelets · doi:10.1080/09537104.2016.1203396 · Cited by 24
Advances in the cell biology of the trafficking and processing of amyloid precursor protein: impact of familial Alzheimer's disease mutations
Wang, J., Fourrière, L., & Gleeson, P. A. (2024) · Biochemical Journal · doi:10.1042/bcj20240056 · Cited by 26
Amyloid β: Walking on the dark side of the moon
Fedele, E., Rivera, D., Marengo, B., Pronzato, M. A., & Ricciarelli, R. (2015) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2015.09.001 · Cited by 23
“Unfortunately, the real identity of α-secretase is still to be established, although it would appear to be a metalloprotease of the ADAM family (Hooper and Turner, 2002; Kuhn et al., 2010).”
Background
Understanding the complexity of the matrix metalloproteinase system and its relevance to age-related diseases: Age-related macular degeneration and Alzheimer's disease
Hussain, A. A., Lee, Y., & Marshall, J. (2019) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2019.100775 · Cited by 26
The regulatory mechanism and therapeutic potential of transcription factor EB in neurodegenerative diseases
Jiao, F., Zhou, B., & Meng, L. (2022) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.13985 · Cited by 21
Role of BRI2 in Dementia
del Campo, M., & Teunissen, C. E. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-131364 · Cited by 23
Surface expression and limited proteolysis of ADAM10 are increased by a dominant negative inhibitor of dynamin
Carey, R. M., Blusztajn, J. K., & Slack, B. E. (2011) · BMC Cell Biology · doi:10.1186/1471-2121-12-20 · Cited by 23
“Moreover, APP shedding is nearly abolished in primary neurons from mice null for ADAM10 [38], and in cell lines following knockdown of ADAM10 [39], indicating that ADAM10 is the physiologically relevant a-secretase in brain.”
Background
Role of prostacyclin signaling in endothelial production of soluble amyloid precursor protein-α in cerebral microvessels
He, T., Santhanam, A. V. R., Lü, T., d’Uscio, L. V., & Katušić, Z. S. (2015) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x15618977 · Cited by 23
Effects of senescence and angiotensin II on expression and processing of amyloid precursor protein in human cerebral microvascular endothelial cells
Sun, R., He, T., Pan, Y., & Katušić, Z. S. (2018) · Aging · doi:10.18632/aging.101362 · Cited by 25
“The mechanisms of APP processing by ADAM9 are not fully understood [42, 48].”
Background
Proximity ligation assay reveals both pre- and postsynaptic localization of the APP-processing enzymes ADAM10 and BACE1 in rat and human adult brain
Lundgren, J. L., Vandermeulen, L., Matton, A., Ahmed, S., Winblad, B. G., Luca, M. D., Tjernberg, L. O., Marcello, E. E., & Frykman, S. (2020) · BMC Neuroscience · doi:10.1186/s12868-020-0554-0 · Cited by 23
“On the other hand, ADAM10 also cleaves substrates which are located both pre- and postsynaptically as well as transsynaptically [14].”
Stimulation of Non-Amyloidogenic Processing of Amyloid-β Protein Precursor by Cryptotanshinone Involves Activation and Translocation of ADAM10 and PKC-α
Durairajan, S. S. K., Liu, L., Lu, J., Koo, I., Maruyama, K., Chung, S. K., Huang, J., & Li, M. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-102085 · Cited by 23
Characterization of β-secretase inhibitory peptide purified from skate skin protein hydrolysate
Lee, J. K., Li‐Chan, E. C. Y., & Byun, H. (2014) · European Food Research and Technology · doi:10.1007/s00217-014-2314-9 · Cited by 22
“Generally, APP disassembling occurs constitutively by α- and β-secretases and leads to the secretion of soluble APP (APPs) [4].”
Background
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
Cystatin C Shifts APP Processing from Amyloid-β Production towards Non-Amyloidgenic Pathway in Brain Endothelial Cells
Wang, X., Liu, D., Liang, Y., Xing, L.-L., Zhao, W.-H., Qin, X., Shang, D., Li, B., Fang, W., Cao, L., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0161093 · Cited by 22
“ADAM10, a transmembrane metalloprotease, has been demonstrated as the major α-secretase producing sAPPα [29,30].”
Background
FMRP Regulates the Nuclear Export of Adam9 and Psen1 mRNAs: Secondary Analysis of an N6-Methyladenosine Dataset
Westmark, C. J., Maloney, B., Alisch, R. S., Sokol, D. K., & Lahiri, D. K. (2020) · Scientific Reports · doi:10.1038/s41598-020-66394-y · Cited by 23
Role and Functions of Irisin: A Perspective on Recent Developments and Neurodegenerative Diseases
Minuti, A., Raffaele, I., Scuruchi, M., Lui, M., Muscarà, C., & Calabrò, M. (2025) · Antioxidants · doi:10.3390/antiox14050554 · Cited by 27
“This was achieved through the suppression of NLRP3 inflammasome activation and its downstream effectors, such as caspase-1 and GSDMD. Irisin also alleviated oxidative stress induced by α -syn PFFs, decreasing malondialdehyde (MDA) levels and restoring SOD and glutathione (GSH) levels, along with…”
A cellular model of amyloid precursor protein processing and amyloid-β peptide production
Macias, M. P., Gonzales, A. M., Siniard, A. L., Walker, A. W., Corneveaux, J. J., Huentelman, M. J., Sabbagh, M. N., & Decourt, B. (2013) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2013.11.024 · Cited by 21
“Alternatively, an α-secretasemediated cleavage of APP can occur within the precursor protein’s Aβ peptide sequence, precluding Aβ production (Kuhn et al., 2010).”
Background
APP-BACE1 Interaction and Intracellular Localization Regulate Aβ Production in iPSC-Derived Cortical Neurons
Roselli, S., Şatır, T. M., Camacho, R., Fruhwürth, S., Bergström, P., Zetterberg, H., & Agholme, L. (2023) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-023-01374-0 · Cited by 24
Alpha-lipoic acid alleviates cognitive deficits in transgenic APP23/PS45 mice through a mitophagy-mediated increase in ADAM10 α-secretase cleavage of APP
Zhang, J., Jiang, Y., Dong, X., Meng, Z., Ji, L., Kang, Y., Liu, M., Zhou, W., & Song, W. (2024) · Alzheimer s Research & Therapy · doi:10.1186/s13195-024-01527-3 · Cited by 23
Bioinformatics Identification of Modules of Transcription Factor Binding Sites in Alzheimer′s Disease‐Related Genes by In Silico Promoter Analysis and Microarrays
Augustin, R., Lichtenthaler, S. F., Greeff, M., Hansen, J., Wurst, W., & Trümbach, D. (2011) · International Journal of Alzheimer s Disease · doi:10.4061/2011/154325 · Cited by 23
Self-citation
Calcium-Sensing Receptor Antagonist NPS 2143 Restores Amyloid Precursor Protein Physiological Non-Amyloidogenic Processing in Aβ-Exposed Adult Human Astrocytes
Chiarini, A., Armato, U., Liu, D., & Prà, I. D. (2017) · Scientific Reports · doi:10.1038/s41598-017-01215-3 · Cited by 21
Multifaceted Roles of Metzincins in CNS Physiology and Pathology: From Synaptic Plasticity and Cognition to Neurodegenerative Disorders
Brzdąk, P., Nowak, D., Wiera, G., & Mozrzymas, J. W. (2017) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2017.00178 · Cited by 21
“Among the ADAM family, ADAM10 (but not ADAM9 or ADAM17) has particularly strong constitutive α-secretase activity in vivo (Kuhn et al., 2010).”
Background
Non‐cell‐autonomous function of DR6 in Schwann cell proliferation
Colombo, A. V., Hsia, H., Wang, M., et al. (2018) · The EMBO Journal · doi:10.15252/embj.201797390 · Cited by 21
“Lentiviral particles were purified as previously described (Kuhn et al , 2010) with minor modifications.”
InfluentialSelf-citation
Enhancing α-secretase Processing for Alzheimer’s Disease—A View on SFRP1
Tang, B. L. (2020) · Brain Sciences · doi:10.3390/brainsci10020122 · Cited by 21
“If APP is first subjected to cleavage by an α-secretase [10], such as a disintegrin and metalloproteinase (ADAM)10 [11,12] or the tumor necrosis factor-alpha converting enzyme (TACE/ADAM17) [13], the BACE1 recognition site is disrupted and the subsequent γ-secretase cleavage does not produce Aβ (see Figure 1).”
Background
Spatiotemporal processing of neural cell adhesion molecules 1 and 2 by BACE1 in vivo
Kim, W., Watanabe, H., Lomoio, S., & Tesco, G. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.100372 · Cited by 21
“Lichtenthaler) (111), anti-β-tubulin (rabbit pAb, 1:1000; 2146; Cell Signaling), anti-BACE1 (rabbit mAb, 1:1500; D10E5; Cell signaling); anti-CHL1 (goat pAb, 1:2000; AF2147; R&D systems); anti-calnexin (mouse mAb, 1:1000; 610523; BD biosciences); anti-GAPDH (mouse mAb, 1:10,000; MAP374; Millipore), anti-PSD95 (rabbit…”
The Transcriptional Regulatory Properties of Amyloid Beta 1–42 may Include Regulation of Genes Related to Neurodegeneration
Gezen‐Ak, D., Atasoy, İ. L., Candaş, E., Alaylıoğlu, M., & Dursun, E. (2018) · NeuroMolecular Medicine · doi:10.1007/s12017-018-8498-6 · Cited by 21
Structural Determinant of β-Amyloid Formation: From Transmembrane Protein Dimerization to β-Amyloid Aggregates
Papadopoulos, N., Suelves, N., Perrin, F., Vadukul, D. M., Vrancx, C., Constantinescu, S. N., & Kienlen-Campard, P. (2022) · Biomedicines · doi:10.3390/biomedicines10112753 · Cited by 20
“The main α-secretase for APP is ADAM10 [60], while studies suggest that TACE is the preferred α-secretase of APLP2 [61].”
Background
Alzheimer’s Disease, Drosophila melanogaster and Polyphenols
Jiménez-Del-Río, M., & Velez‐Pardo, C. (2015) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-18365-7_2 · Cited by 21
Shedding light on prion disease
Glatzel, M., Linsenmeier, L., Dohler, F., Krasemann, S., Puig, B., & Altmeppen, H. C. (2015) · Prion · doi:10.1080/19336896.2015.1065371 · Cited by 22
The Association of Amyloid-β Protein Precursor With α- and β-Secretases in Mouse Cerebral Cortex Synapses Is Altered in Early Alzheimer’s Disease
Pliássova, A., Lopes, J. P., Lemos, C., Oliveira, C. R., Cunha, R. A., & Agostinho, P. M. (2015) · Molecular Neurobiology · doi:10.1007/s12035-015-9491-9 · Cited by 21
Characterisation of acetylcholinesterase release from neuronal cells
Hicks, D. A., Makova, N. Z., Nalivaeva, N. N., & Turner, A. J. (2012) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2012.09.019 · Cited by 20
Acute Effects of Muscarinic M1 Receptor Modulation on AβPP Metabolism and Amyloid-β Levels in vivo : A Microdialysis Study
Welt, T., Kulic, L., Hoey, S. E., McAfoose, J., Späni, C. B., Chadha, A. S., Fisher, A., & Nitsch, R. M. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-150152 · Cited by 18
Amyloid-β precursor protein processing and oxidative stress are altered in human iPSC-derived neuron and astrocyte co-cultures carrying presenillin-1 gene mutations following spontaneous differentiation
Elsworthy, R. J., King, M. C., Grainger, A. I., Fisher, E., Crowe, J. A., Alqattan, S., Ludlam, A., Hill, E. J., & Aldred, S. (2021) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2021.103631 · Cited by 19
The Swedish dilemma - the almost exclusive use of APPswe-based mouse models impedes adequate evaluation of alternative β-secretases
Armbrust, F., Bickenbach, K., Marengo, L., Pietrzik, C. U., & Becker‐Pauly, C. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2021.119164 · Cited by 21
The Amyloid Precursor Protein Represses Expression of Acetylcholinesterase in Neuronal Cell Lines
Hicks, D. A., Makova, N. Z., Gough, M., Parkin, E. T., Nalivaeva, N. N., & Turner, A. J. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.461269 · Cited by 20
Role of Amyloid-β–Metal Interactions In Alzheimer‘s Disease
Duce, J. A., Bush, A. I., & Adlard, P. A. (2011) · Future Neurology · doi:10.2217/fnl.11.43 · Cited by 20
Dysregulated expression of miR-140 and miR-122 compromised microglial chemotaxis and led to reduced restriction of AD pathology
Song, C., Li, S., Mai, Y., Li, L., Dai, G., Zhou, Y., Liang, X., Zou, O. M., Wang, Y., Zhou, L., et al. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03162-z · Cited by 19
“ADAM10, a member of ADAM (a disintegrin and metalloprotease) family, is the main α-secretase that cleaves APP in brain [17, 18].”
Background
BACE1-cleavage of Sez6 and Sez6L is elevated in Niemann-Pick type C disease mouse brains
Čaušević, M., Dominko, K., Malnar, M., Vidatic, L., Čermak, S., Pigoni, M., Kuhn, P., Colombo, A. V., Havas, D., Flunkert, S., et al. (2018) · PLoS ONE · doi:10.1371/journal.pone.0200344 · Cited by 20
Self-citation
Harpertrioate A, an A,B,D-seco-Limonoid with Promising Biological Activity against Alzheimer’s Disease from Twigs of Harrisonia perforata (Blanco) Merr.
Tang, X., Luo, R., Ye, M.-S., et al. (2020) · Organic Letters · doi:10.1021/acs.orglett.0c03460 · Cited by 19
Differential expression of ADAM15 and ADAM17 metalloproteases in the rat brain after severe hypobaric hypoxia and hypoxic preconditioning
Rybnikova, E. A., Gluschenko, T. S., Galeeva, A., Tyulkova, E. I., Nalivaeva, N. N., Makova, N. Z., Turner, A. J., & Самойлов, М. О. (2012) · Neuroscience Research · doi:10.1016/j.neures.2011.12.010 · Cited by 20
Recent Understanding of the Molecular Mechanisms of Alzheimer?s Disease
Grimm, M. O. W., & Hartmann, T. (2011) · Journal of Addiction Research & Therapy · doi:10.4172/2155-6105.s5-004 · Cited by 20
Aβ1-15/16 as a Potential Diagnostic Marker in Neurodegenerative Diseases
Nutu, M., Bourgeois, P., Zetterberg, H., Portelius, E., Andréasson, U., Parent, S., Lipari, F., Hall, S., Constantinescu, R., Hansson, O., et al. (2012) · NeuroMolecular Medicine · doi:10.1007/s12017-012-8208-8 · Cited by 19
Seismic behavior of cable‒stayed bridges: a review
Cámara, A. (2018) · MOJ Civil Engineering · doi:10.15406/mojce.2018.04.00115 · Cited by 18
Nmnat2 attenuates amyloidogenesis and up-regulates ADAM10 in AMPK activity-dependent manner
Cheng, X., Shi, F.-X., Zhao, K.-P., Lin, W., Li, X.-Y., Zhang, J., Bu, Y.-Y., Zhu, R., Li, X.-H., Duan, D.-X., et al. (2021) · Aging · doi:10.18632/aging.203634 · Cited by 18
“ADAM10 is the valid active component of α-secretase [15, 16].”
Background
Constitutive Cleavage of the Single-Pass Transmembrane Protein Alcadeinα Prevents Aberrant Peripheral Retention of Kinesin-1
Maruta, C., Saito, Y., Hata, S., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0043058 · Cited by 18
“APP is a well-characterized single-pass type I transmembrane protein that undergoes constitutive cleavage by ADAM10 [17], and its AP fusion protein was previously shown to be cleaved and secreted similar to wild-type APP [18].”
Background
Huatuo Zaizao pill ameliorates cognitive impairment of APP/PS1 transgenic mice by improving synaptic plasticity and reducing Aβ deposition
Zhang, J., Yu, L., Yang, H., Hui, Z., Jiang, S., Chen, L., Zhao, Y., Wang, S., Liu, Y., & Xu, Y. (2018) · BMC Complementary and Alternative Medicine · doi:10.1186/s12906-018-2237-2 · Cited by 18
“This is considered an important mechanism preventing the generation of the Alzheimer’s disease Aβ peptide (Aβ) [43, 44].”
Background
Tyrosine O-GalNAc Alters the Conformation and Proteolytic Susceptibility of APP Model Glycopeptides
Singh, Y., Ormaza, D., Massetti, A., et al. (2021) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.1c00387 · Cited by 17
Revisiting APP secretases: an overview on the holistic effects of retinoic acid receptor stimulation in APP processing
Vitória, J. J. M., Trigo, D., & Silva, O. A. B. D. C. E. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-04090-4 · Cited by 19
“The anti-amyloidogenic α-secretase A Disintegrin And Metalloproteinase (ADAM) domain-containing protein 10 (ADAM10) is a relevant α-secretase with constitutive activity that directly competes for APP at the cell surface [45].”
Background
The role of ADAM10 in astrocytes: Implications for Alzheimer’s disease
Elsworthy, R. J., Hill, E. J., Dunleavy, C., & Aldred, S. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.1056507 · Cited by 17
“As the major α-secretase responsible for APP processing, ADAM10 has been of significant interest in AD (Postina et al., 2004; Kuhn et al., 2010).”
Background
Calmodulin and Amyloid Beta as Coregulators of Critical Events during the Onset and Progression of Alzheimer’s Disease
O’Day, D. H. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24021393 · Cited by 17
“The CaMBP ADAM10 is involved in redirecting AβPP1 processing along the non-amyloidogenic pathway [31].”
Background
Treadmill workout activates PPARα in the hippocampus to upregulate ADAM10, decrease plaques and improve cognitive functions in 5XFAD mouse model of Alzheimer’s disease
Rangasamy, S. B., Jana, M., Dasarathi, S., Kundu, M., & Pahan, K. (2023) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2023.01.009 · Cited by 18
Important functional role of residue x of the presenilin Gx GD protease active site motif for APP substrate cleavage specificity and substrate selectivity of γ‐secretase
Kretner, B., Fukumori, A., Kuhn, P., Pérez‐Revuelta, B. I., Lichtenthaler, S. F., Haass, C., & Steiner, H. (2012) · Journal of Neurochemistry · doi:10.1111/jnc.12124 · Cited by 18
Self-citation
Multidisciplinary approaches for targeting the secretase protein family as a therapeutic route for Alzheimer's disease
Schaduangrat, N., Prachayasittikul, V., Choomwattana, S., Wongchitrat, P., Phopin, K., Suwanjang, W., Malik, A. A., Vincent, B., & Nantasenamat, C. (2019) · Medicinal Research Reviews · doi:10.1002/med.21563 · Cited by 17
“Finally, it has more recently been shown that ADAM10 is the principal relevant physiological α‐secretase of βAPP in primary cortical neurons.(55) Numerous convincing evidence have been observed for the PKC‐regulated α cleavage of βAPP and is for a large part carried out by ADAM17 (also termed TACE for TNFα‐Converting…”
Background
Levistolide A Attenuates Alzheimer's Pathology Through Activation of the PPARγ Pathway
Qu, X., Guan, P., Han, L., Wang, Z., & Huang, X. (2020) · Neurotherapeutics · doi:10.1007/s13311-020-00943-1 · Cited by 18
PPARα Modulation-Based Therapy in Central Nervous System Diseases
Lee, D., Tomita, Y., Allen, W., Tsubota, K., Negishi, K., & Kurihara, T. (2021) · Life · doi:10.3390/life11111168 · Cited by 17
LRP1 Modulates APP Intraneuronal Transport and Processing in Its Monomeric and Dimeric State
Herr, U.-M., Strecker, P., Storck, S. E., Thomas, C., Rabiej, V. K., Junker, A., Schilling, S., Schmidt, N., Dowds, C. M., Eggert, S., et al. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00118 · Cited by 17
“It has been well documented over the last decade that ADAM10 is the most prominent sheddase of APP at the cell surface (Weidemann et al., 1989; Lammich et al., 1999; Jorissen et al., 2010; Kuhn et al., 2010).”
Background
α-secretase ADAM10 physically interacts with β-secretase BACE1 in neurons and regulates CHL1 proteolysis
Wang, X., Wang, C., & Pei, G. (2018) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjy001 · Cited by 17
Current Drug Targets in Alzheimer’s Associated Memory Impairment: A Comprehensive Review
Chandrashekar, K. S., Mathew, A., Vignesh Balaji, E., Pai, K. S. R., Kishore, A., Pai, V., & Pemmireddy, R. (2022) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527321666220401124719 · Cited by 18
Transmembrane Amyloid-Related Proteins in CSF as Potential Biomarkers for Alzheimer’s Disease
López‐Font, I., Cuchillo‐Ibáñez, I., Sogorb‐Esteve, A., García‐Ayllón, M., & Sáez‐Valero, J. (2015) · Frontiers in Neurology · doi:10.3389/fneur.2015.00125 · Cited by 16
“Evidence indicates that ADAM10, but not ADAM9 or ADAM17, is the enzyme acting as a physiologically relevant constitutive α-secretase in vivo (46, 47).”
Background
Marginal Vitamin A Deficiency Exacerbates Memory Deficits Following A?1-42 Injection in Rats
Zeng, J., Li, T., Gong, M., Jiang, W., Yang, T., Chen, J., Liu, Y., & Chen, L. (2017) · Current Alzheimer Research · doi:10.2174/1567205013666161223162110 · Cited by 17
“The reduction of a disintegrin and metalloprotease 10 (ADAM10), the central component of α-secretase, promotes AD pathogenesis by shifting α-cleavage to β -cleavage of APP [5].”
BackgroundInfluential
Extracellular-Signal-Regulated Kinase Inhibition Switches APP Processing from β- to α-Secretase under Oxidative Stress: Modulation of ADAM10 by SIRT1/NF-κB Signaling
Thonda, S., Puttapaka, S. N., Kona, S. V., & Kalivendi, S. V. (2021) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.1c00582 · Cited by 16
DC2 and Keratinocyte-associated Protein 2 (KCP2), Subunits of the Oligosaccharyltransferase Complex, Are Regulators of the γ-Secretase-directed Processing of Amyloid Precursor Protein (APP)
Wilson, C. M., Magnaudeix, A., Yardin, C., & Terro, F. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.249748 · Cited by 17
The impact of capsaicinoids on APP processing in Alzheimer’s disease in SH-SY5Y cells
Grimm, M. O. W., Blümel, T., Lauer, A. A., Janitschke, D., Stahlmann, C. P., Mett, J., Haupenthal, V. J., Miederer, A.-M., Niemeyer, B. A., Grimm, H. S., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-66009-6 · Cited by 15
Spatial–Temporal Mapping Reveals the Golgi as the Major Processing Site for the Pathogenic Swedish APP Mutation: Familial APP Mutant Shifts the Major APP Processing Site
Wang, J., Gleeson, P. A., & Fourrière, L. (2024) · Traffic · doi:10.1111/tra.12932 · Cited by 17
ADAM10-Initiated Release of Notch Intracellular Domain Regulates Microtubule Stability and Radial Migration of Cortical Neurons
Yang, Z. H., Li, P.-F., Chen, R., Wang, J., Wang, S., Shen, Y., Wu, X., Fang, B., Cheng, X., & Xiong, Z. (2017) · Cerebral Cortex · doi:10.1093/cercor/bhx006 · Cited by 15
“…the major protease for extracellular cleavage of transmembrane targets such as Notch, APP, and N-Cadherin (Hartmann et al. 2002; Reiss et al. 2005; Kuhn et al. 2010), while does ADAM10-initiated RIP of these proteins remain conserved in migrating neurons needs further examination, since the RIP…”
Sulfuretin exerts diversified functions in the processing of amyloid precursor protein
Chen, J., Luo, B., Zhong, B., Li, K., Wen, Q., Li, S., Xiang, X., Zhou, G., Hu, L., Deng, X., et al. (2020) · Genes & Diseases · doi:10.1016/j.gendis.2020.11.008 · Cited by 16
“On the other hand, ADAM10 silencing decreases a-CTF and sAPPa levels with the slight increase of Ab level in SH-SY5Y cells and murine cultured neurons where APP was not overexpressed.(58) Overexpression of ADAM10 in mice promotes the generation of a-CTF and sAPPa and reduces Ab load.”
Background
C6 Glioma-Secreted NGF and FGF2 Regulate Neuronal APP Processing Through Up-Regulation of ADAM10 and Down-Regulation of BACE1, Respectively
Xie, H., Xiao, Z., & Huang, J. (2015) · Journal of Molecular Neuroscience · doi:10.1007/s12031-015-0690-7 · Cited by 15
“a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) (Lammich et al. 1999; Kuhn et al. 2010) initiates cleavage of APP followed by cleavage with γ-secretase.”
Background
Idebenone Decreases Aβ Pathology by Modulating RAGE/Caspase-3 Signaling and the Aβ Degradation Enzyme NEP in a Mouse Model of AD
Lee, H., Jeong, H.-R., Park, J.-H., & Hoe, H. (2021) · Biology · doi:10.3390/biology10090938 · Cited by 15
“For instance, knockdown of ADAM10 decreases sAPPα levels in mouse primary cortical neuronal cells [6], and in HEK293 APPswe cells, L-isoaspartyl O-methyltransferase knockdown decreases ADAM10/17 expression, thereby enhancing Aβ40 levels [7].”
Background
The Biochemistry and Physiology of A Disintegrin and Metalloproteinases (ADAMs and ADAM-TSs) in Human Pathologies
Sharma, D., & Singh, N. K. (2021) · Reviews of physiology, biochemistry and pharmacology · doi:10.1007/112_2021_67 · Cited by 16
Amyloid-β Oligomers Regulate ADAM10 Synaptic Localization Through Aberrant Plasticity Phenomena
Marcello, E. E., Musardo, S., Vandermeulen, L., Pelucchi, S., Gardoni, F., Santo, N., Antonucci, F., & Luca, M. D. (2019) · Molecular Neurobiology · doi:10.1007/s12035-019-1583-5 · Cited by 14
The Amyloid Cascade Hypothesis 2.0: On the Possibility of Once-in-a-Lifetime-Only Treatment for Prevention of Alzheimer’s Disease and for Its Potential Cure at Symptomatic Stages
Volloch, V., & Rits‐Volloch, S. (2022) · Journal of Alzheimer s Disease Reports · doi:10.3233/adr-220031 · Cited by 15
Altering APP Proteolysis: Increasing sAPPalpha Production by Targeting Dimerization of the APP Ectodomain
Libeu, C. P., Descamps, O., Zhang, Q., John, V., & Bredesen, D. E. (2012) · PLoS ONE · doi:10.1371/journal.pone.0040027 · Cited by 15
“To confirm that disulfiram binding disrupts the dimer interface of the fusion protein and changes the accessibility of the a-cleavage site to proteolysis, MBP-eAPP230–624 was probed using ADAM10, a physiologically relevant alpha-secretase candidate protease involved in the production of sAPPa [43].”
Molecular aspects of the pathogenesis and current approaches to pharmacological correction of Alzheimer’s disease
Kukharsky, M. S., Овчинников, Р. К., & Бачурин, С. О. (2015) · S S Korsakov Journal of Neurology and Psychiatry · doi:10.17116/jnevro20151156103-114 · Cited by 15
Overexpression of MTERF4 promotes the amyloidogenic processing of APP by inhibiting ADAM10
Wang, X., Liu, Q., Chen, G., Li, M., & Ding, Y. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.11.135 · Cited by 13
Secretases-related miRNAs in Alzheimer’s disease: new approach for biomarker discovery
Hajjari, S. N., Mehdizadeh, M., Sadigh‐Eteghad, S., Shanehbandi, D., Teimourian, S., & Baradaran, B. (2017) · Neurological Sciences · doi:10.1007/s10072-017-3086-3 · Cited by 13
Proteolytically generated soluble Tweak Receptor Fn14 is a blood biomarker for γ‐secretase activity
Güner, G., Aßfalg, M., Zhao, K., Dreyer, T. F., Lahiri, S., Lo, Y., Slivinschi, B. I., Imhof, A., Jocher, G., Strohm, L., et al. (2022) · EMBO Molecular Medicine · doi:10.15252/emmm.202216084 · Cited by 13
Self-citation
Possible involvement of endoplasmic reticulum stress in the pathogenesis of Alzheimer’s disease
Hosoi, T., Nomura, J., Ozawa, K., Nishi, A., & Nomura, Y. (2015) · Endoplasmic Reticulum Stress in Diseases · doi:10.1515/ersc-2015-0008 · Cited by 14
“ADAM10 is previously shown to increase sAPP-α levels [66, 67], which also protects against neuronal death [6870].”
Background
Increased Foxo3a Nuclear Translocation and Activity is an Early Neuronal Response to βγ-Secretase-Mediated Processing of the Amyloid-β Protein Precursor: Utility of an AβPP-GAL4 Reporter Assay
Law, B. M., Guest, A. L., Pullen, M. W. J., Perkinton, M. S., & Williams, R. J. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-170393 · Cited by 13
“TAPI is a broad spectrum non-selective inhibitor and the constitutive (cid:4) -secretase in neurons is most likely ADAM10 [39], so the effect of a more selective ADAM10 inhibitor (GI 254023X) was also investigated.”
Functional Amyloids and their Possible Influence on Alzheimer Disease
Lau, A., Bourkas, M. E. C., Lu, Y. Q. Q., Ostrowski, L., Weber‐Adrian, D., Figueiredo, C., Arshad, H., Shoaei, S. Z. S., Morrone, C. D., Matan‐Lithwick, S. A., et al. (2017) · Discoveries · doi:10.15190/d.2017.9 · Cited by 13
Self-citation
Regulation of the Soluble Amyloid Precursor Protein α (sAPPα) Levels by Acetylcholinesterase and Brain-Derived Neurotrophic Factor in Lung Cancer Cell Media
Khashali, H. A., Ray, R., Coleman, K.-L., Atali, S., Haddad, B., Wareham, J., Guthrie, J. W., Heyl, D., & Evans, H. G. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231810746 · Cited by 13
NeuroAiD® (MLC601) and Amyloid Precursor Protein Processing
Lim, Y.-A., Murray, L. A., Lai, M. K. P., & Chen, C. (2013) · Cerebrovascular Diseases · doi:10.1159/000346236 · Cited by 12
Evidence for a clathrin-independent endocytic pathway for APP internalization in the neuronal somatodendritic compartment
Aow, J., Huang, T.-R., Goh, Y. T., Sun, A. X., Thinakaran, G., & Koo, E. H. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112774 · Cited by 12
Construction of an Exudative Age-Related Macular Degeneration Diagnostic and Therapeutic Molecular Network Using Multi-Layer Network Analysis, a Fuzzy Logic Model, and Deep Learning Techniques: Are Retinal and Brain Neurodegenerative Disorders Related?
Latifi‐Navid, H., Behrooz, A. B., Jamehdor, S., Davari, M., Latifinavid, M., Zolfaghari, N., Piroozmand, S., Taghizadeh, S., Bourbour, M., Shemshaki, G., et al. (2023) · Pharmaceuticals · doi:10.3390/ph16111555 · Cited by 13
PKC Activation Counteracts ADAM10 Deficit in HuD-Silenced Neuroblastoma Cells
Marchesi, N., Amadio, M., Colombrita, C., Govoni, S. M., Ratti, A., & Pascale, A. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160299 · Cited by 12
“PP) [26, 27], represents a target of nELAV RBP, whose binding is disrupted by A (cid”
Transcriptional repression of the ectodomain sheddase ADAM10 by TBX2 and potential implication for Alzheimer’s disease
Reinhardt, S., Schuck, F., Stoye, N. M., Hartmann, T., Grimm, M. O. W., Pflugfelder, G. O., & Endres, K. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2998-2 · Cited by 13
Shifting the balance: soluble ADAM10 as a potential treatment for Alzheimer's disease
Hershkovits, A. S., Gelley, S., Hanna, R., Kleifeld, O., Shulman, A., & Fishman, A. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1171123 · Cited by 12
“Surface-presented APP of neuronal cells was endogenously shed by membrane-bound ADAM10 (Lammich et al., 1999; Kuhn et al., 2010).”
Background
Upregulation of sFRP1 Is More Profound in Female than Male 5xFAD Mice and Positively Associated with Amyloid Pathology
Macyczko, J. R., Wang, N., Lü, W., Jeevaratnam, S., Shue, F., Martens, Y. A., Liu, C., Kanekiyo, T., Bu, G., & Li, Y. (2023) · Journal of Alzheimer s Disease · doi:10.3233/jad-230218 · Cited by 11
“PP in neurons [4, 5].”

Authors: Kuhn, P., Wang, H., Dislich, B., Colombo, A., Zeitschel, U., Ellwart, J. W., Kremmer, E., Roßner, S., & Lichtenthaler, S. F.
Affiliations: Adolf-Butenandt-Institut für Physiologische Chemie, Physikalische Biochemie und Zellbiologie (DE)
German Center for Neurodegenerative Diseases (DE)
Leipzig University (DE)
Helmholtz Munich (DE)
Corresponding author: Lichtenthaler, Stefan F
ORCID: Kuhn, Peer‐Hendrik
Wang, Huanhuan
Dislich, Bastian
Colombo, Alessio
Roßner, Steffen
Lichtenthaler, Stefan F
Venue: The EMBO Journal
Publisher: Springer Science and Business Media LLC
Published: 2010-07-30
Volume: 29
Issue: 17
Pages: 3020-3032
ISSN: 0261-4189 (ISSN-L)
1460-2075
DOI: 10.1038/emboj.2010.167
PMC: PMC2944055
OpenAlex: W2137592631
Semantic Scholar: dffd3996f14fbf65316cf86b6f725026d299c98e
Cited by: 621
References: 55
Citations by year: 2026: 19 · 2025: 17 · 2024: 27 · 2023: 32 · 2022: 37 · 2021: 42 · 2020: 41 · 2019: 46 · 2018: 47 · 2017: 42 · 2016: 42 · 2015: 42 · 2014: 44 · 2013: 44 · 2012: 49
FWCI: 30.98
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: The EMBO Journal (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Site cant be reached (submittedVersion)
DZNE Pub (submittedVersion)
Funders: Deutsche Forschungsgemeinschaft (SFB 596, SFB596 project B12, project Z2))
Bundesministerium für Bildung und Forschung (SFB596)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords: ADAM10, alpha-secretase, amyloid precursor protein, APP processing, amyloid-beta, beta-secretase, gamma-secretase, ADAM9, ADAM17, primary neurons, Alzheimer's disease
MeSH terms: ADAM10 Protein, Animals, Cell Line, Humans, Membrane Proteins, Neurons, Mass Spectrometry, Amyloid beta-Protein Precursor, Mice, ADAM Proteins, Amyloid Precursor Protein Secretases

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

ADAM10 is the physiologically relevant, constitutive α‐secretase of the amyloid precursor protein in primary neurons

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks