A disintegrin-metalloproteinase prevents amyloid plaque formation and hippocampal defects in an Alzheimer disease mouse model

Postina, Rolf; Schroeder, Anja; Dewachter, Ilse; Bohl, Juergen; Schmitt, Ulrich; Kojro, Elzbieta; Prinzen, Claudia; Endres, Kristina; Hiemke, Christoph; Blessing, Manfred; Flamez, Pascaline; Dequenne, Antoine; Godaux, Emile; van Leuven, Fred; Fahrenholz, Falk

doi:10.1172/jci20864

Cited by 638Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

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A disintegrin-metalloproteinase prevents amyloid plaque formation and hippocampal defects in an Alzheimer disease mouse model

Postina, Rolf, Schroeder, Anja, Dewachter, Ilse, Bohl, Juergen, Schmitt, Ulrich, Kojro, Elzbieta, Prinzen, Claudia, Endres, Kristina, Hiemke, Christoph, Blessing, Manfred, Flamez, Pascaline, Dequenne, Antoine, Godaux, Emile, van Leuven, Fred, Fahrenholz, Falk·2004·Journal of Clinical Investigation

DOI 10.1172/jci20864

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Abstract

Alzheimer disease (AD) is characterized by excessive deposition of amyloid beta-peptides (A beta peptides) in the brain. In the nonamyloidogenic pathway, the amyloid precursor protein (APP) is cleaved by the alpha-secretase within the A beta peptide sequence. Proteinases of the ADAM family (adisintegrin and metalloproteinase) are the main candidates as physiologically relevant alpha-secretases, but early lethality of knockout animals prevented a detailed analysis in neuronal cells. To overcome this restriction, we have generated transgenic mice that overexpress either ADAM10 or a catalytically inactive ADAM10 mutant. In this report we show that a moderate neuronal overexpression of ADAM10 in mice transgenic for human APP([V717I]) increased the secretion of the neurotrophic soluble alpha-secretase-released N-terminal APP domain (APPs alpha), reduced the formation of A beta peptides, and prevented their deposition in plaques. Functionally, impaired long-term potentiation and cognitive deficits were alleviated. Expression of mutant catalytically inactive ADAM10 led to an enhancement of the number and size of amyloid plaques in the brains of double-transgenic mice. The results provide the first in vivo evidence for a proteinase of the ADAM family as an alpha-secretase of APP, reveal activation of ADAM10 as a promising therapeutic target, and support the hypothesis that a decrease in alpha-secretase activity contributes to the development of AD.

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GDE2 is required to control neuronal ADAM10 α-secretase activity.
“these observations support the model that GDE2 is required to control neuronal ADAM10 α-secretase activity.”
From GDE2-RECK controls ADAM10 α-secretase–mediated cleavage of amyloid precursor protein (2021) · cites this paper as [30]
The Discussion (p. 7) reports that neuronal overexpression of ADAM10 increases α-secretase cleavage of APP. The paper does not establish the claim's central point that GDE2 is required to control that activity; a search for GDE2 found no passage addressing it. (LLM, conf=0.86)
Experimental — accuracy not yet measured
α-secretase cleavage of APP by ADAM10 is inversely related to BACE1 mediated β-secretase cleavage.
“However, the α-secretase cleavage of APP by ADAM10 has also been shown to be inversely related to BACE1 mediated β-secretase cleavage [101, 102, 136].”
From Global identification of neuronal and astrocytic integral membrane proteins that require Retromer for their endosomal recycling (2026) · cites this paper as [136]
Overexpression of ADAM10 in mouse models can halt Aβ production and subsequent aggregation.
“Overexpression of ADAM10 in mouse models can halt Aβ production and subsequent aggregation69.”
From Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing (2019) · cites this paper as [69]
Moderate neuronal overexpression of ADAM10 in transgenic AD mice increased sAPPα levels and decreased Aβ, with reduction of deficits in long-term potentiation and learning.
“These data linking sAPPα to neuroprotection were later confirmed by studies showing that moderate neuronal overexpression of ADAM10 in transgenic AD mice favored an increase in sAPPα levels and a decrease in Aβ, concomitant with a reduction of deficits in long-term potentiation (LTP) and learning (Postina et al., 2004).”
From Emerging Alternative Proteinases in APP Metabolism and Alzheimer’s Disease Pathogenesis: A Focus on MT1-MMP and MT5-MMP (2019) · cites this paper as Postina et al., 2004

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Paxinos, G. (2001) · Cited by 12,859
Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359
Developments of a water-maze procedure for studying spatial learning in the rat
Morris, R. (1984) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(84)90007-4 · Cited by 7,180
A Laboratory manual
Ashburner, M. (1989) · Cold Spring Harbor Laboratory eBooks · Cited by 6,756
Alzheimer's Disease: Genes, Proteins, and Therapy
Selkoe, D. J. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.2.741 · Cited by 6,063
Manipulating the mouse embryo: A laboratory manual
Hogan, B. L. M., Costantini, F. D., & Lacy, E. (1986) · Cited by 4,460
Naturally secreted oligomers of amyloid β protein potently inhibit hippocampal long-term potentiation in vivo
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
Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis
Kayed, R., Head, E., Thompson, J. L., McIntire, T. M., Milton, S. C., Cotman, C. W., & Glabe, C. G. (2003) · Science · doi:10.1126/science.1079469 · Cited by 4,064
Applications of the Morris water maze in the study of learning and memory
D’Hooge, R., & Deyn, P. P. D. (2001) · Brain Research Reviews · doi:10.1016/s0165-0173(01)00067-4 · Cited by 2,083
Purification and cloning of amyloid precursor protein β-secretase from human brain
Sinha, S., Anderson, J. P., Barbour, R., Basi, G. S., Caccavello, R., Davis, D., Doan, M., Dovey, H. F., Frigon, N., Hong, J., et al. (1999) · Nature · doi:10.1038/990114 · Cited by 1,612
Formation of Neurofibrillary Tangles in P301L Tau Transgenic Mice Induced by Aβ42 Fibrils
Götz, J., Chen, F., van Dorpe, J., & Nitsch, R. M. (2001) · Science · doi:10.1126/science.1062097 · Cited by 1,526
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
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
Self-citation
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
Targeting of cell-surface β-amyloid precursor protein to lysosomes: alternative processing into amyloid-bearing fragments
Haass, C., Koo, E. H., Mellon, A., Hung, A. Y., & Selkoe, D. J. (1992) · Nature · doi:10.1038/357500a0 · Cited by 919
Hes1 and Hes5 as Notch effectors in mammalian neuronal differentiation
Ohtsuka, T., Ishibashi, M., Gradwohl, G., Nakanishi, S., Guillemot, F., & Kageyama, R. (1999) · The EMBO Journal · doi:10.1093/emboj/18.8.2196 · Cited by 852
Low cholesterol stimulates the nonamyloidogenic pathway by its effect on the α-secretase ADAM 10
Kojro, E., Gimpl, G., Lammich, S., März, W., & Fahrenholz, F. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.081612998 · Cited by 804
Self-citation
A learning deficit related to age and β-amyloid plaques in a mouse model of Alzheimer's disease
Chen, G., Chen, K. S., Knox, J., Inglis, J., Bernard, A., Martin, S. J., Justice, A., McConlogue, L., Games, D., Freedman, S. B., et al. (2000) · Nature · doi:10.1038/35050103 · Cited by 740
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
Enhanced Proteolysis of β-Amyloid in APP Transgenic Mice Prevents Plaque Formation, Secondary Pathology, and Premature Death
Leissring, M. A., Farris, W., Chang, A. Y., Walsh, D. M., Wu, X., Sun, X., Frosch, M. P., & Selkoe, D. J. (2003) · Neuron · doi:10.1016/s0896-6273(03)00787-6 · Cited by 725
The disintegrin/metalloprotease ADAM 10 is essential for Notch signalling but not for alpha-secretase activity in fibroblasts
Hartmann, D. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.21.2615 · Cited by 680
Early Phenotypic Changes in Transgenic Mice That Overexpress Different Mutants of Amyloid Precursor Protein in Brain
Moechars, D., Dewachter, I., Lorent, K., Reversé, D., Baekelandt, V., Naidu, A., Tesseur, I., Spittaels, K., Haute, C. V. D., Checler, F., et al. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.10.6483 · Cited by 668
Self-citation
Aging renders the brain vulnerable to amyloid β-protein neurotoxicity
Guela, C., Wu, C.-K., Saroff, D., Lorenzo, A., Yuan, M., & Yankner, B. A. (1998) · Nature Medicine · doi:10.1038/nm0798-827 · Cited by 520
Regulated Cleavage of a Contact-Mediated Axon Repellent
Hattori, M., Osterfield, M., & Flanagan, J. G. (2000) · Science · doi:10.1126/science.289.5483.1360 · Cited by 518
Relative Abundance of Alzheimer A Beta Amyloid Peptide Variants in Alzheimer Disease and normal Aging
Näslund, J., Schierhorn, A., Hellman, U., Lannfelt, L., Roses, A. D., Tjernberg, L. O., Silberring, J., Gandy, S. E., Winblad, B., & Greengard, P. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.18.8378 · Cited by 468
Increased Activity‐Regulating and Neuroprotective Efficacy of α‐Secretase‐Derived Secreted Amyloid Precursor Protein Conferred by a C‐Terminal Heparin‐Binding Domain
Furukawa, K., Sopher, B. L., Rydel, R. E., Begley, J. G., Pham, D. G., Martin, G. M., Fox, M., & Mattson, M. P. (1996) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1996.67051882.x · Cited by 414
Maturation and Endosomal Targeting of β-Site Amyloid Precursor Protein-cleaving Enzyme
Huse, J. T., Pijak, D. S., Leslie, G. J., Lee, V. M.-Y., & Doms, R. W. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m004175200 · Cited by 402
A heparin-binding domain in the amyloid protein precursor of Alzheimer's disease is involved in the regulation of neurite outgrowth
Small, D. H., Nurcombe, V., Reed, G., Clarris, H. J., Moir, R. D., Beyreuther, K. T., & Masters, C. L. (1994) · Journal of Neuroscience · doi:10.1523/jneurosci.14-04-02117.1994 · Cited by 394
Ectodomain shedding of L1 adhesion molecule promotes cell migration by autocrine binding to integrins
Mechtersheimer, S., Gutwein, P., Agmon-Levin, N., Stoeck, A., Oleszewski, M., Riedle, S., Postina, R., Fahrenholz, F., Fogel, M., Lemmon, V., et al. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.200101099 · Cited by 391
Self-citation
Memory-enhancing effects of secreted forms of the β-amyloid precursor protein in normal and amnestic mice
Méziane, H., Dodart, J., Mathis, C., Little, S. H., Clemens, J. A., Paul, S. M., & Ungerer, A. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.21.12683 · Cited by 379
Aβ-Generating Enzymes
Vassar, R. J., & Citron, M. (2000) · Neuron · doi:10.1016/s0896-6273(00)00051-9 · Cited by 299
Membrane-anchored metalloprotease MDC9 has an α-secretase activity responsible for processing the amyloid precursor protein
KOIKE, H., Tomioka, S., Sorimachi, H., Saido, T. C., Maruyama, K., Okuyama, A., Fujisawa‐Sehara, A., Ohno, S., Suzuki, K., & Ishiura, S. (1999) · Biochemical Journal · doi:10.1042/bj3430371 · Cited by 290
Neuronal Deficiency of Presenilin 1 Inhibits Amyloid Plaque Formation and Corrects Hippocampal Long-Term Potentiation But Not a Cognitive Defect of Amyloid Precursor Protein [V717I] Transgenic Mice
Dewachter, I., Reversé, D., Caluwaerts, N., Ris, L., Kuipéri, C., den Haute, C. V., Spittaels, K., Umans, L., Serneels, L., Thiry, E., et al. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-09-03445.2002 · Cited by 236
Self-citation
Chemical characterization of A beta 17-42 peptide, a component of diffuse amyloid deposits of Alzheimer disease
Gowing, E., Roher, A. E., Woods, A. S., Cotter, R. J., Chaney, M., Little, S. P., & Ball, M. J. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)78080-6 · Cited by 223
Prominent Cerebral Amyloid Angiopathy in Transgenic Mice Overexpressing the London Mutant of Human APP in Neurons
Dorpe, J. V., Smeijers, L., Dewachter, I., Nuyens, D., Spittaels, K., den Haute, C. V., Mercken, M. H., Moechars, D., Laenen, I., Kuipéri, C., et al. (2000) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64644-5 · Cited by 223
Self-citation
Brain plasmin enhances APP α‐cleavage and Aβ degradation and is reduced in Alzheimer's disease brains
Ledesma, M. D., Silva, J. S. D., Craessaerts, K., Delacourte, A., Strooper, B. D., & Dotti, C. G. (2000) · EMBO Reports · doi:10.1093/embo-reports/kvd107 · Cited by 216
In vivo reduction of amyloid-β by a mutant copper transporter
Phinney, A. L., Drisaldi, B., Schmidt, S. D., Lugowski, S. J., Coronado, V. A., Liang, Y., Horne, P., Yang, J., Sekoulidis, J., Coomaraswamy, J., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2332851100 · Cited by 204
Cleavage of Alzheimer's Amyloid Precursor Protein by α-Secretase Occurs at the Surface of Neuronal Cells
Parvathy, S., Hussain, I., Karran, E. H., Turner, A. J., & Hooper, N. M. (1999) · Biochemistry · doi:10.1021/bi9906827 · Cited by 200
Intravenous nonviral gene therapy causes normalization of striatal tyrosine hydroxylase and reversal of motor impairment in experimental parkinsonism.
Zhang, Y., Calon, F., Zhu, C., Boado, R. J., & Pardridge, W. M. (2003) · Human Gene Therapy · doi:10.1089/10430340360464660 · Cited by 194
Levels of α- and β-secretase cleaved amyloid precursor protein in the cerebrospinal fluid of Alzheimer's disease patients
Sennvik, K., Fastbom, J., Blomberg, M. E., Wahlund, L., Winblad, B., & Benedikz, E. (2000) · Neuroscience Letters · doi:10.1016/s0304-3940(99)00929-5 · Cited by 193
Coordinated Expression of β‐Amyloid Precursor Protein and the Putative β‐Secretase BACE and α‐Secretase ADAM10 in Mouse and Human Brain
Marcinkiewicz, M. M., & Seidah, N. G. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0752133.x · Cited by 190
Signaling Events in Amyloid β-Peptide-induced Neuronal Death and Insulin-like Growth Factor I Protection
Wei, W., Wang, X., & Kusiak, J. W. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111704200 · Cited by 190
Secreted form of β-amyloid precursor protein shifts the frequency dependency for induction of LTD, and enhances LTP in hippocampal slices
Ishida, A., Furukawa, K., Keller, J. N., & Mattson, M. P. (1997) · Neuroreport · doi:10.1097/00001756-199707070-00009 · Cited by 177
Endogenous Serine Protease Inhibitor Modulates Epileptic Activity and Hippocampal Long-Term Potentiation
Lüthi, A., van der Putten, H., Botteri, F., Mansuy, I., Meins, M., Frey, U., Sansig, G., Portet, C., Schmutz, M., Schröder, M. S., et al. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-12-04688.1997 · Cited by 176
Decreased α-secretase-cleaved amyloid precursor protein as a diagnostic marker for Alzheimer's diseas
Lannfelt, L., Basun, H., Wahlund, L., Rowe, B. A., & Wagner, S. L. (1995) · Nature Medicine · doi:10.1038/nm0895-829 · Cited by 173
Abeta 17-42 in Alzheimer's disease activates JNK and caspase-8 leading to neuronal apoptosis
Wei, W. (2002) · Brain · doi:10.1093/brain/awf205 · Cited by 155
In search of a better mouse test.
Wahlsten, D., Rustay, N., Metten, P., & Crabbe, J. (2003) · Trends in Neurosciences · doi:10.1016/s0166-2236(03)00033-x · Cited by 149
Characterization of New Polyclonal Antibodies Specific for 40 and 42 Amino Acid-Long Amyloid β Peptides: Their Use to Examine the Cell Biology of Presenilins and the Immunohistochemistry of Sporadic Alzheimer’s Disease and Cerebral Amyloid Angiopathy Cases
Barelli, H., Lebeau, A., Vizzavona, J., Delaère, P., Chevallier, N., Drouot, C., Marambaud, P., Ancolio, K., Buxbaum, J. D., Khorkova, O., et al. (1997) · Molecular Medicine · doi:10.1007/bf03401708 · Cited by 143
The Search for α-Secretase and its Potential as a Therapeutic Approach to Alzheimer's Disease
Hooper, N. M., & Turner, A. J. (2002) · Current Medicinal Chemistry · doi:10.2174/0929867023370121 · Cited by 127
The Neuronal Adaptor Protein X11α Reduces Aβ Levels in the Brains of Alzheimer's APPswe Tg2576 Transgenic Mice
Lee, J., Lau, K., Perkinton, M. S., Standen, C. L., Shemilt, S. J. A., Mercken, L., Cooper, J. D., McLoughlin, D. M., & Miller, C. C. J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300503200 · Cited by 83
P3 beta-amyloid peptide has a unique and potentially pathogenic immunohistochemical profile in Alzheimer's disease brain.
Higgins, L. S., Murphy, G. M., Forno, L. S., Catalano, R., & Cordell, B. (1996) · Europe PMC (PubMed Central) · Cited by 70
Reduced cerebrospinal fluid levels of α-secretase-cleaved amyloid precursor protein in aged rats: correlation with spatial memory deficits
Anderson, J. J., Höltz, G., Baskin, P. P., Wang, R., Mazzarelli, L., Wagner, S. L., & Menzaghi, F. (1999) · Neuroscience · doi:10.1016/s0306-4522(99)00244-4 · Cited by 62
New Amide-Bearing Benzolactam-Based Protein Kinase C Modulators Induce Enhanced Secretion of the Amyloid Precursor Protein Metabolite sAPPα
Kozikowski, A. P., Nowak, I., Petukhov, P. A., et al. (2002) · Journal of Medicinal Chemistry · doi:10.1021/jm020350r · Cited by 47
[23] Membrane-associated metalloproteinase recognized by characteristic cleavage of myelin basic protein: Assay and isolation
Howard, L., & Glynn, P. (1995) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(95)48025-0 · Cited by 44
The amyloid β‐protein precursor of Alzheimer's disease is degraded extracellularly by a Kunitz protease inhibitor domain‐sensitive trypsin‐like serine protease in cultures of chick sympathetic neurons
Caswell, M. D., Mok, S. S., Henry, A., et al. (1999) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.1999.00886.x · Cited by 18
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Kuhn, P., Wang, H., Dislich, B., Colombo, A., Zeitschel, U., Ellwart, J. W., Kremmer, E., Roßner, S., & Lichtenthaler, S. F. (2010) · The EMBO Journal · doi:10.1038/emboj.2010.167 · Cited by 621
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Willem, M., Tahirovic, S., Busche, M. A., Ovsepian, S. V., Chafai, M., Kootar, S., Hornburg, D., Evans, L. D. B., Moore, S., Daria, A., et al. (2015) · Nature · doi:10.1038/nature14864 · Cited by 398
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Roberts, B. R., Ryan, T. M., Bush, A. I., Masters, C. L., & Duce, J. A. (2012) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07500.x · Cited by 266
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The role of tetraspanins in the regulation of the A Disintegrin and Metalloprotease 10 (ADAM10)
Seipold, L. (2017) · MACAU: Open Access Repository of Kiel University (University Library Kiel)
The transmembrane domain of the amyloid precursor protein is required for antiamyloidogenic processing by α-secretase ADAM10
Hitschler, L., & Lang, T. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.101911 · Cited by 11
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Small, D. H. (2002) · Peptides · doi:10.1016/s0196-9781(02)00072-4 · Cited by 11
P4–267: ADAM10 activation is required for green tea EGCG–induced alpha–secretase cleavage of amyloid precursor protein
Tan, J., Obregon, D. F., Rezai-Zadeh, K. P., et al. (2006) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2006.05.2006 · Cited by 4

Authors: Postina, R., Schroeder, A., Dewachter, I., Bohl, J., Schmitt, U., Kojro, E., Prinzen, C., Endres, K., Hiemke, C., Blessing, M., Flamez, P., Dequenne, A., Godaux, E., van Leuven, F., & Fahrenholz, F.
Affiliations: Johannes Gutenberg University Mainz (DE)
KU Leuven (BE)
University of Mons (BE)
Corresponding author: Fahrenholz, Falk
ORCID: Dewachter, Ilse
Schmitt, Ulrich
Endres, Kristina
Hiemke, Christoph
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2004-05-15
Volume: 113
Issue: 10
Pages: 1456-1464
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci20864
OpenAlex: W2132810311
Cited by: 638
References: 56
Citations by year: 2026: 6 · 2025: 7 · 2024: 19 · 2023: 25 · 2022: 18 · 2021: 30 · 2020: 26 · 2019: 31 · 2018: 29 · 2017: 34 · 2016: 34 · 2015: 34 · 2014: 37 · 2013: 39 · 2012: 31
FWCI: 20.82
Type: journal article
Language: en
Open access: closed
Locations: Journal of Clinical Investigation (publishedVersion)
PubMed (publishedVersion)
Funders: Deutsche Forschungsgemeinschaft
Fonds Wetenschappelijk Onderzoek
Fritz Thyssen Stiftung
KU Leuven
Vlaamse regering
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: Alzheimer's disease, ADAM10, alpha-secretase, amyloid-beta, amyloid plaques, amyloid precursor protein, soluble APP alpha, long-term potentiation, cognitive impairment, hippocampus, non-amyloidogenic pathway, therapeutic target
MeSH terms: Alzheimer Disease, Amyloid, Amyloidosis, Animals, Disease Models, Animal, Hippocampus, Humans, Mice, Transgenic, Endopeptidases, Gene Expression, Aspartic Acid Endopeptidases, Amyloid beta-Protein Precursor, Mice, Amyloid Precursor Protein Secretases

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A disintegrin-metalloproteinase prevents amyloid plaque formation and hippocampal defects in an Alzheimer disease mouse model

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