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BACE inhibition-dependent repair of Alzheimer’s pathophysiology
Open accessAbstract
Significance The accumulation of amyloid-β (Aβ) proteins in the brain contributes to Alzheimer´s disease (AD). Reducing Aβ by inhibiting its production with a β-secretase (BACE) inhibitor represents a novel mechanism for treating AD; however, whether this therapeutic strategy is capable of repairing impaired brain circuits associated with AD is unknown. Here we demonstrate that BACE inhibition is beneficial to all levels of impairment in an AD mouse model: cellular, long-range circuitry, and memory. We provide evidence that the rescue is dependent on the reduction of soluble forms of Aβ surrounding amyloid plaques. These results have mechanistic and therapeutic implications for AD, including Aβ-related memory defects.
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“which has been shown to be dependent on soluble Aβ [38–40]”
From Selective suppression of oligodendrocyte-derived amyloid beta rescues neuronal dysfunction in Alzheimer’s disease (2024) · cites this paper as [38]
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Cites
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
The amyloid hypothesis of Alzheimer's disease at 25 years
Selkoe, D. J., & Hardy, J. (2016) · EMBO Molecular Medicine · doi:10.15252/emmm.201606210 · Cited by 6,164
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 · cited 1×
“NB-360 inhibits the enzymatic activity of BACE, which is required for the generation of Aβ peptides from APP (12).”
BackgroundShankar, G. M., Li, S., Mehta, T. H., Garcia-Munoz, A., Shepardson, N. E., Smith, I., Brett, F. M., Farrell, M. A., Rowan, M. J., Lemere, C. A., et al. (2008) · Nature Medicine · doi:10.1038/nm1782 · Cited by 3,685
Two Phase 3 Trials of Bapineuzumab in Mild-to-Moderate Alzheimer's Disease
Salloway, S., Sperling, R., Fox, N. C., Blennow, K., Klunk, W., Raskind, M., Sabbagh, M., Honig, L. S., Porsteinsson, A. P., Ferris, S., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1304839 · Cited by 1,960
Masters, C. L., Bateman, R., Blennow, K., Rowe, C. C., Sperling, R. A., & Cummings, J. L. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.56 · Cited by 1,853
Citron, M., Oltersdorf, T., Haass, C., McConlogue, L., Hung, A. Y., Seubert, P., Vigo-Pelfrey, C., Lieberburg, I., & Selkoe, D. J. (1992) · Nature · doi:10.1038/360672a0 · Cited by 1,757
A mutation in APP protects against Alzheimer’s disease and age-related cognitive decline
Jonsson, T., Atwal, J. K., Steinberg, S., Snaedal, J., Jonsson, P. V., Bjornsson, S., Stefansson, H., Sulem, P., Gudbjartsson, D., Maloney, J., et al. (2012) · Nature · doi:10.1038/nature11283 · Cited by 1,738
Phase 3 Trials of Solanezumab for Mild-to-Moderate Alzheimer's Disease
Doody, R. S., Thomas, R. G., Farlow, M., Iwatsubo, T., Vellas, B., Joffe, S., Kieburtz, K., Raman, R., Sun, X., Aisen, P. S., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1312889 · Cited by 1,668
Amyloid-β–induced neuronal dysfunction in Alzheimer's disease: from synapses toward neural networks
Palop, J. J., & Mucke, L. (2010) · Nature Neuroscience · doi:10.1038/nn.2583 · Cited by 1,651
Clusters of Hyperactive Neurons Near Amyloid Plaques in a Mouse Model of Alzheimer’s Disease
Busche, M. A., Eichhoff, G., Adelsberger, H., Abramowski, D., Wiederhold, K.-H., Haass, C., Staufenbiel, M., Konnerth, A., & Garaschuk, O. (2008) · Science · doi:10.1126/science.1162844 · Cited by 1,125
Self-citationNeuronal activity regulates the regional vulnerability to amyloid-β deposition
Bero, A. W., Yan, P., Roh, J. H., Cirrito, J. R., Stewart, F. R., Raichle, M. E., Lee, J.-M., & Holtzman, D. M. (2011) · Nature Neuroscience · doi:10.1038/nn.2801 · Cited by 880
Koffie, R. M., Meyer-Luehmann, M., Hashimoto, T., Adams, K. W., Mielke, M. L., Garcia-Alloza, M., Micheva, K. D., Smith, S. J., Kim, M. L., Lee, V. M., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0811698106 · Cited by 850
Oddo, S., Billings, L., Kesslak, J. P., Cribbs, D. H., & LaFerla, F. M. (2004) · Neuron · doi:10.1016/j.neuron.2004.07.003 · Cited by 780
Busche, M. A., Chen, X., Henning, H. A., Reichwald, J., Staufenbiel, M., Sakmann, B., & Konnerth, A. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1206171109 · Cited by 715
Self-citationThree dimensions of the amyloid hypothesis: time, space and 'wingmen'
Musiek, E. S., & Holtzman, D. M. (2015) · Nature Neuroscience · doi:10.1038/nn.4018 · Cited by 662
β-amyloid disrupts human NREM slow waves and related hippocampus-dependent memory consolidation
Mander, B. A., Marks, S. M., Vogel, J. W., Rao, V., Lu, B., Saletin, J. M., Ancoli-Israel, S., Jagust, W. J., & Walker, M. P. (2015) · Nature Neuroscience · doi:10.1038/nn.4035 · Cited by 569
Kennedy, M. E., Stamford, A. W., Chen, X., Cox, K., Cumming, J. N., Dockendorf, M. F., Egan, M. F., Ereshefsky, L., Hodgson, R. A., Hyde, L. A., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aad9704 · Cited by 441
Astrocytes in physiological aging and Alzheimer’s disease
Rodríguez-Arellano, J. J., Parpura, V., Zorec, R., & Verkhratsky, A. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2015.01.007 · Cited by 439
η-Secretase processing of APP inhibits neuronal activity in the hippocampus
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 · cited 1×
“These peptides can effectively promote neuronal silencing and impair hippocampal long-term potentiation in mice (31).”
BackgroundSelf-citationImpairments of neural circuit function in Alzheimer's disease
Busche, M. A., & Konnerth, A. (2016) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2015.0429 · Cited by 360
Self-citationYang, T., Li, S., Xu, H., Walsh, D. M., & Selkoe, D. J. (2017) · The Journal of Neuroscience · doi:10.1523/jneurosci.1698-16.2016 · Cited by 347
Putcha, D., Brickhouse, M. J., O’Keefe, K., Sullivan, C., Rentz, D. M., Marshall, G. A., Dickerson, B. C., & Sperling, R. A. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.4740-11.2011 · Cited by 268
Neuronal hyperactivity--A key defect in Alzheimer’s disease?
Busche, M. A., & Konnerth, A. (2015) · BioEssays · doi:10.1002/bies.201500004 · Cited by 266
Self-citationCharacterizing the Appearance and Growth of Amyloid Plaques in APP/PS1 Mice
Yan, P., Bero, A. W., Cirrito, J. R., Xiao, Q., Hu, X., Wang, Y., Gonzales, E., Holtzman, D. M., & Lee, J.-M. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.2637-09.2009 · Cited by 264
Making Waves: Initiation and Propagation of Corticothalamic Ca2+ Waves In Vivo
Stroh, A., Adelsberger, H., Groh, A., Rühlmann, C., Fischer, S., Schierloh, A., Deisseroth, K. A., & Konnerth, A. (2013) · Neuron · doi:10.1016/j.neuron.2013.01.031 · Cited by 249
Self-citationChronic Optogenetic Activation Augments Aβ Pathology in a Mouse Model of Alzheimer Disease
Yamamoto, K., Tanei, Z., Hashimoto, T., Wakabayashi, T., Okuno, H., Naka, Y., Yizhar, O., Fenno, L. E., Fukayama, M., Bito, H., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.04.017 · Cited by 225
Rescue of long-range circuit dysfunction in Alzheimer's disease models
Busche, M. A., Kekuš, M., Adelsberger, H., Noda, T., Förstl, H., Nelken, I., & Konnerth, A. (2015) · Nature Neuroscience · doi:10.1038/nn.4137 · Cited by 221
Self-citationMay, P. C., Willis, B. A., Lowe, S. L., Dean, R. A., Monk, S. A., Cocke, P. J., Audia, J. E., Boggs, L. N., Borders, A. R., Brier, R. A., et al. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.4129-14.2015 · Cited by 206
BACE1 Physiological Functions May Limit Its Use as Therapeutic Target for Alzheimer's Disease
Barão, S., Moechars, D., Lichtenthaler, S. F., & De Strooper, B. (2016) · Trends in Neurosciences · doi:10.1016/j.tins.2016.01.003 · Cited by 158
Das, P., Murphy, M. P., Younkin, L. H., Younkin, S. G., & Golde, T. E. (2001) · Neurobiology of Aging · doi:10.1016/s0197-4580(01)00245-7 · Cited by 150
Decreased amyloid-β and increased neuronal hyperactivity by immunotherapy in Alzheimer's models
Busche, M. A., Grienberger, C., Keskin, A. D., Song, B., Neumann, U., Staufenbiel, M., Förstl, H., & Konnerth, A. (2015) · Nature Neuroscience · doi:10.1038/nn.4163 · Cited by 146
Self-citationStaged decline of neuronal function in vivo in an animal model of Alzheimer's disease
Grienberger, C., Rochefort, N. L., Adelsberger, H., Henning, H. A., Hill, D. N., Reichwald, J., Staufenbiel, M., & Konnerth, A. (2012) · Nature Communications · doi:10.1038/ncomms1783 · Cited by 138
Self-citationNeuropathology after active Aβ42 immunotherapy: implications for Alzheimer’s disease pathogenesis
Boche, D., Denham, N., Holmes, C., & Nicoll, J. A. R. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0719-5 · Cited by 135
Maier, F. C., Wehrl, H. F., Schmid, A. M., Mannheim, J. G., Wiehr, S., Lerdkrai, C., Calaminus, C., Stahlschmidt, A., Ye, L., Burnet, M. W. M., et al. (2014) · Nature Medicine · doi:10.1038/nm.3734 · Cited by 122
Self-citationHippocampal activation is associated with longitudinal amyloid accumulation and cognitive decline
Leal, S. L., Landau, S. M., Bell, R. K., & Jagust, W. J. (2017) · eLife · doi:10.7554/elife.22978 · Cited by 117
Neumann, U., Rueeger, H., Machauer, R., Veenstra, S. J., Lueoend, R. M., Tintelnot-Blomley, M., Laue, G., Beltz, K., Vogg, B., Schmid, P., et al. (2015) · Molecular Neurodegeneration · doi:10.1186/s13024-015-0033-8 · Cited by 113
Self-citationAttenuation of β-Amyloid Deposition and Neurotoxicity by Chemogenetic Modulation of Neural Activity
Yuan, P., & Grutzendler, J. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.2531-15.2016 · Cited by 112
Impairment of in vivo calcium signaling in amyloid plaque-associated microglia
Brawek, B., Schwendele, B., Riester, K., Kohsaka, S., Lerdkrai, C., Liang, Y., & Garaschuk, O. (2014) · Acta Neuropathologica · doi:10.1007/s00401-013-1242-2 · Cited by 108
Shimshek, D. R., Jacobson, L. H., Kolly, C., Zamurovic, N., Balavenkatraman, K. K., Morawiec, L., Kreutzer, R., Schelle, J., Jucker, M., Bertschi, B., et al. (2016) · Scientific Reports · doi:10.1038/srep21917 · Cited by 69
Self-citationIn vivo calcium imaging of the aging and diseased brain
Eichhoff, G., Busche, M. A., & Garaschuk, O. (2008) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-007-0709-6 · Cited by 59
Self-citationMably, A. J., Liu, W., Donald, J. M. M., Dodart, J., Bard, F., Lemere, C. A., O’Nuallain, B., & Walsh, D. M. (2015) · Neurobiology of Disease · doi:10.1016/j.nbd.2015.07.008 · Cited by 55
Imaging microcircuit function in healthy and diseased brain
Garaschuk, O. (2012) · Experimental Neurology · doi:10.1016/j.expneurol.2012.02.009 · Cited by 24
Alain De Cheveigné, A., Edeline, J., Gaucher, Q., & Gourévitch, B. (2012) · Journal of Neurophysiology · doi:10.1152/jn.00040.2012 · Cited by 20
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The Amyloid-β Oligomer Hypothesis: Beginning of the Third Decade
Cline, E. N., Bicca, M. A., Viola, K. L., & Klein, W. L. (2018) · Journal of Alzheimer's Disease · doi:10.3233/jad-179941 · Cited by 870
A vicious cycle of β amyloid−dependent neuronal hyperactivation
Zott, B., Simon, M. M., Hong, W., Unger, F., Chen-Engerer, H.-J., Frosch, M. P., Sakmann, B., Walsh, D. M., & Konnerth, A. (2019) · Science · doi:10.1126/science.aay0198 · Cited by 640
Self-citationTau impairs neural circuits, dominating amyloid-β effects, in Alzheimer models in vivo
Busche, M. A., Wegmann, S., Dujardin, S., Commins, C., Schiantarelli, J., Klickstein, N., Kamath, T. V., Carlson, G. A., Nelken, I., & Hyman, B. T. (2019) · Nature Neuroscience · doi:10.1038/s41593-018-0289-8 · Cited by 413
Self-citationBACE1 inhibitors: Current status and future directions in treating Alzheimer's disease
Moussa‐Pacha, N. M., Abdin, S. M., Omar, H. A., Alniss, H., & Al‐Tel, T. H. (2020) · Medicinal Research Reviews · doi:10.1002/med.21622 · Cited by 274
Metadata
- Authors
- Keskin, A. D., Kekuš, M., Adelsberger, H., Neumann, U., Shimshek, D. R., Song, B., Zott, B., Peng, T., Förstl, H., Staufenbiel, M., Nelken, I., Sakmann, B., Konnerth, A., & Busche, M. A.
- Affiliations
- Technical University of Munich (DE)
- Novartis (Switzerland) (CH)
- Helmholtz Munich (DE)
- Hertie Institute for Clinical Brain Research (DE)
- Hebrew University of Jerusalem (IL)
- Munich Cluster for Systems Neurology (DE)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2017-07-24
- Volume
- 114
- Issue
- 32
- Pages
- 8631-8636
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5559049
- OpenAlex
- W2738200982
- Cited by
- 125
- References
- 44
- Citations by year
- 2026: 2 · 2025: 10 · 2024: 19 · 2023: 11 · 2022: 10 · 2021: 19 · 2020: 13 · 2019: 28 · 2018: 13
- FWCI
- 10.93
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- mediaTUM (Technical University of Munich) (submittedVersion)
- Site cant be reached (submittedVersion)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
- Funders
- EC | FP7 | FP7 Ideas: European Research Council (Advanced Grant)
- 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, beta-secretase inhibitors, amyloid-beta, amyloid plaques, soluble amyloid-beta, memory impairment, AD mouse model
- MeSH terms
- Alzheimer Disease, Animals, Disease Models, Animal, Humans, Mice, Transgenic, Neurons, Protease Inhibitors, Amyloid beta-Peptides, Mice, Amyloid Precursor Protein Secretases
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