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A subset of NSAIDs lower amyloidogenic Aβ42 independently of cyclooxygenase activity
Abstract
Epidemiological studies have documented a reduced prevalence of Alzheimer's disease among users of nonsteroidal anti-inflammatory drugs (NSAIDs). It has been proposed that NSAIDs exert their beneficial effects in part by reducing neurotoxic inflammatory responses in the brain, although this mechanism has not been proved. Here we report that the NSAIDs ibuprofen, indomethacin and sulindac sulphide preferentially decrease the highly amyloidogenic Abeta42 peptide (the 42-residue isoform of the amyloid-beta peptide) produced from a variety of cultured cells by as much as 80%. This effect was not seen in all NSAIDs and seems not to be mediated by inhibition of cyclooxygenase (COX) activity, the principal pharmacological target of NSAIDs. Furthermore, short-term administration of ibuprofen to mice that produce mutant beta-amyloid precursor protein (APP) lowered their brain levels of Abeta42. In cultured cells, the decrease in Abeta42 secretion was accompanied by an increase in the Abeta(1-38) isoform, indicating that NSAIDs subtly alter gamma-secretase activity without significantly perturbing other APP processing pathways or Notch cleavage. Our findings suggest that NSAIDs directly affect amyloid pathology in the brain by reducing Abeta42 peptide levels independently of COX activity and that this Abeta42-lowering activity could be optimized to selectively target the pathogenic Abeta42 species.
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“Anti-inflammatory drugs such as NSAIDs have been used as a potential treatment in AD because of their capacity to bind to and stimulate the nuclear receptor peroxisome proliferator-activated receptor (PPAR)-γ as well as their direct effects on the amyloid formation [101].”
From Chemical Constituents and Pharmacological Activities of Garlic (Allium sativum L.): A Review (2020) · cites this paper as [101]
In the citing paper
“The first GSMs were discovered by recognizing that ibuprofen, indomethacin and sulindac reduce Abeta42 levels (Weggen et al., 2001) through modulation of gamma-secretase activity (Eriksen et al., 2003).”
From Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (2019) · cites this paper as Weggen et al., 2001
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“Modification of the purification protocol using water precipitation followed by removal of scavengers by washing with diethyl ether circumvented the need for HPLC purification and provided these peptides with purity as high as HPLC-purified peptides and substantially increased yield.”
MethodExploring the chemical space of γ-secretase modulators
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Self-citationPrevention strategies for Alzheimer’s disease
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“Research indicates that ROCKs are potential therapeutic targets for Aβ metabolism modulation (Weggen et al., 2001; Jacobs et al., 2006; Salminen et al., 2008).”
Siskou, I. C., Rekka, E. A., Kourounakis, A. P., Chrysselis, M. C., Tsiakitzis, K., & Kourounakis, P. N. (2006) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2006.10.056 · Cited by 26
Signal Peptide Peptidase and γ-Secretase Share Equivalent Inhibitor Binding Pharmacology
Iben, L. G., Olson, R. E., Balanda, L. A., Jayachandra, S., Robertson, B., Hay, V., Corradi, J., Prasad, C. V. C., Zaczek, R. C., Albright, C. F., et al. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m707002200 · Cited by 26
Imaging and In Vivo Quantitation of β-Amyloid: An Exemplary Biomarker for Alzheimer’s Disease?
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γ-Secretase Modulation with Aβ42-Lowering Nonsteroidal Anti-Inflammatory Drugs and Derived Compounds
Czirr, E., & Weggen, S. (2006) · Neurodegenerative Diseases · doi:10.1159/000095270 · Cited by 28
“These findings raise the possibility of prohibitive side effects in human clinical trials and indicate that, at a minimum, clinical dosing of γ-secretase inhibitors will need to be adjusted to allow residual NOTCH signaling in the periphery.As Aβ42 seems to be the key pathogenic agent that initiates the neurodegenerat…”
BackgroundSelf-citationPharmacotherapy for Alzheimer's Disease: 2002
Knopman, D. S. (2003) · Clinical Neuropharmacology · doi:10.1097/00002826-200303000-00009 · Cited by 26
“A recent laboratorybased investigation of NSAIDs concluded that some of these agents may decrease A production (64).”
BackgroundNSAIDs and Alzheimer's disease: how far to generalise from trials?
Breitner, J. C. S. (2003) · The Lancet Neurology · doi:10.1016/s1474-4422(03)00498-8 · Cited by 26
Probing Mechanisms and Therapeutic Potential of γ-Secretase in Alzheimer’s Disease
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“These compounds (see Figure 10 for examples) have the effect of lowering Aβ42 levels without decreasing overall Aβ levels or otherwise inhibiting general γ-secretase activity [85,86].”
BackgroundOnce-daily transdermal rivastigmine in the treatment of Alzheimer’s disease
Dodel, R. C. (2008) · Drug Design Development and Therapy · doi:10.2147/dddt.s3102 · Cited by 25
“The protective effect of certain NSAIDs such as indomethacine could be linked to an inhibition of cyclooxygenase and to the processing of β -amyloid precursor protein (Weggen et al 2001).”
Krzystanek, E., Krzystanek, M., Opala, G., Trzeciak, H. I., Siuda, J. S., & Małecki, A. (2007) · Journal of Neural Transmission · doi:10.1007/s00702-007-0669-9 · Cited by 25
“Epidemiological studies have documented a reduced prevalence of AD among users of NSAIDs (indomethacin, ibuprofen) (Lukiw and Bazan, 2000; Weggen et al., 2001 ).”
BackgroundSelective amyloid-β lowering agents
Wolfe, M. S. (2008) · BMC Neuroscience · doi:10.1186/1471-2202-9-s2-s4 · Cited by 27
Effects of medications on plasma amyloid beta (Aβ) 42: Longitudinal data from the VITA cohort
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“The group of NSAIDs was of considerable interest because of in vitro evidence about the lowering effect of certain NSAIDs on Ab42 (Weggen et al., 2001; Eriksen et al., 2003).”
BackgroundJin, D., Sung, J., Hwang, Y. K., Kwon, K. J., Han, S., Min, S. S., & Han, J. (2008) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2008.01.016 · Cited by 25
“Evidence that ibuprofen treatment is beneficial in preventing of AD have arisen from human studies (Tabet and Feldmand, 2003) and animal models of AD (Frautschy et al., 2001; Lim et al., 2000; Weggen et al., 2001).”
BackgroundInflammatory processes and Alzheimer’s disease
Walsh, S. P., & Aisen, P. S. S. (2004) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.4.5.793 · Cited by 25
Asanuma, M., & Miyazaki, I. (2006) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.6.9.1313 · Cited by 28
Honarnejad, K., Daschner, A., Gehring, A. P., Szybińska, A., Giese, A., Kuźnicki, J., Bracher, F., & Herms, J. W. (2014) · Translational Psychiatry · doi:10.1038/tp.2014.132 · Cited by 24
Application of the Neurosphere Assay for DNT Hazard Assessment: Challenges and Limitations
Baumann, J., Dach, K., Barenys, M., Giersiefer, S., Goniwiecha, J., Lein, P. J., & Fritsche, E. (2015) · Methods in pharmacology and toxicology · doi:10.1007/7653_2015_49 · Cited by 24
Lagoja, I. M., Pannecouque, C. C., Griffioen, G., Wera, S., Rojasdelaparra, V. M., & Aerschot, A. A. V. (2011) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2011.05.014 · Cited by 24
“, 2001) or c-secretase modulators (Garofalo, 2008; Serneels et al., 2009; Weggen et al., 2001)] or aiming at increased Ab clearance using antibodies (Gilman et al.”
BackgroundIncreased Cerebrospinal Fluid Aβ38/Aβ42 Ratio in Alzheimer Disease
Mehta, P. D., & Pirttilä, T. (2005) · Neurodegenerative Diseases · doi:10.1159/000090363 · Cited by 24
Inflammation in Alzheimer’s disease
Heneka, M. T. (2006) · Clinical Neuroscience Research · doi:10.1016/j.cnr.2006.09.005 · Cited by 25
-Secretase Modulators: Can We Combine Potency with Safety?
Gijsen, H. J. M., & Mercken, M. H. (2012) · International Journal of Alzheimer s Disease · doi:10.1155/2012/295207 · Cited by 24
“The identification of a subset of NSAIDs as GSMs in 2001 has led to tarenflurbil 2 (Flurizan) as the first NSAID-derived GSM to be tested in the clinic [7, 8].”
BackgroundBacher, M., Dodel, R. C., Aljabari, B., Keyvani, K., Marambaud, P., Kayed, R., Glabe, C. G., Goertz, N., Hoppmann, A., Sachser, N., et al. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20060467 · Cited by 24
Okuda, M., Fujita, Y., Katsube, T., Tabata, H., Yoshino, K., Hashimoto, M., & Sugimoto, H. (2018) · BMC Complementary and Alternative Medicine · doi:10.1186/s12906-018-2167-z · Cited by 24
“HPBR might specifically inhibit the production of Aβ1–42, as some nonsteroidal anti-inflammatory drugs and γ-secretase modulators do [38], but further research is needed to clarify the detailed mechanism.”
BackgroundRosiglitazone improves contextual fear conditioning in aged rats
Gemma, C., Stellwagen, H. M., Fister, M. C., Coultrap, S. J., Mesches, M. H., Browning, M. D., & Bickford, P. C. (2004) · Neuroreport · doi:10.1097/00001756-200410050-00023 · Cited by 24
“Not all NSAIDs, however, induce beneficial effects; the finding that ibuprofen and indomethacin, but not aspirin and naproxen, reduce the production of b-amyloid in cell culture suggests that several mechanisms modulate their actions [9].”
BackgroundPotential novel targets for Alzheimer pharmacotherapy: I. Secretases
Maiorini, A. F., Gaunt, M., Jacobsen, T., McKay, A. E., Waldman, L., & Raffa, R. B. (2002) · Journal of Clinical Pharmacy and Therapeutics · doi:10.1046/j.1365-2710.2002.00415.x · Cited by 24
“It has recently been reported that a subset of NSAIDs may selectively reduce the production of Ab42 (105).”
BackgroundSecond Generation γ-Secretase Modulators Exhibit Different Modulation of Notch β and Aβ Production
Wanngren, J., Ottervald, J., Parpal, S., Portelius, E., Strömberg, K., Borgegård, T., Klintenberg, R., Juréus, A., Blomqvist, J., Blennow, K., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.376541 · Cited by 24
“Both GSMs are known to modulate -secretase activity by shifting the amino acid cleavage from positions 42 to 38 (19, 38), and as expected, we observed a decrease in A 42 accompanied by a relative increase in A 38 compared with untreated cells (Fig.”
BackgroundResultInfluentialCurrent strategies for the treatment of Alzheimer’s disease and other tauopathies
Dickey, C. A., & Petrucelli, L. (2006) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.10.5.665 · Cited by 24
“Over the past 5 – 10 years, progress towards ameliorating AD pathogenesis has made remarkable strides, particularly pertaining to the selective removal of the Aβ42 peptide [3-7].”
Backgroundγ-Secretase: Substrates and Inhibitors
Rochette, M. J., & Murphy, M. P. (2002) · Molecular Neurobiology · doi:10.1385/mn:26:1:081 · Cited by 26
“The multiple conformation hypothesis could similarly explain the existence of compounds and APP mutations that can shift cleavage towards the production of shorter or longer Aβ peptides (40,93,108).”
BackgroundSelf-citationStein, T. D., & Johnson, J. A. (2003) · Reviews in the Neurosciences · doi:10.1515/revneuro.2003.14.4.317 · Cited by 24
Vasudevan, S., Mary, P. V., Vijayakumar, S., & Shankar, R. (2020) · Biophysical Chemistry · doi:10.1016/j.bpc.2020.106394 · Cited by 23
Modulation of γ-Secretase Activity by a Carborane-Based Flurbiprofen Analogue
Saretz, S., Basset, G., Useini, L., Laube, M., Pietzsch, J., Drača, D., Maksimović‐Ivanić, D., Trambauer, J., Steiner, H., & Hey‐Hawkins, E. (2021) · Molecules · doi:10.3390/molecules26102843 · Cited by 23
“(2001) that certain non-steroidal anti-inflammatory drugs (NSAIDs) lead to a reduced production of Aβ42, thereby lowering the Aβ42:Aβ40 ratio in mouse brain and cell culture [9].”
BackgroundCommon Factors of Alzheimer’s Disease and Rheumatoid Arthritis—Pathomechanism and Treatment
Trzeciak, P., Herbet, M., & Dudka, J. (2021) · Molecules · doi:10.3390/molecules26196038 · Cited by 24
“In addition, anti-inflammatory drugs used in the treatment of AD may have a direct influence on secretase activity [125].”
BackgroundKlegeris, A., Maguire, J. A., & McGeer, P. L. (2004) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2004.04.001 · Cited by 23
“The R- and S-enantiomers of flurbiprofen and ibuprofen are equally potent in this property, which is not possessed by several other NSAIDs including naproxen (Weggen et al., 2001).”
BackgroundKimpe, L. D., & Scheper, W. (2009) · Current Medicinal Chemistry · doi:10.2174/092986710790149765 · Cited by 23
“A selection of non-steroid anti-inflammatory drugs (NSAIDs) was demonstrated to modulate rather than inhibit -secretase cleavage resulting in production of a shorter A form that is less prone to aggregation [141].”
BackgroundOfengeim, D., Shi, P., Miao, B., Fan, J., Xia, X., Fan, Y., Lipinski, M. M., Hashimoto, T., Polydoro, M., Yuan, J., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.290957 · Cited by 24
Initial Optimization of a New Series of γ-Secretase Modulators Derived from a Triterpene Glycoside
Fuller, N. O., Hubbs, J. L., Austin, W., Creaser, S. P., McKee, T. D., Loureiro, R. M. B., Tate, B. A., Xia, W., Ives, J. L., Findeis, M. A., et al. (2012) · ACS Medicinal Chemistry Letters · doi:10.1021/ml300256p · Cited by 23
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Self-citationNSAID-Based γ-Secretase Modulators Do Not Bind to the Amyloid-β Polypeptide
Barrett, P. J., Sanders, C. R., Kaufman, S. A., Michelsen, K., & Jordan, J. B. (2011) · Biochemistry · doi:10.1021/bi201371j · Cited by 23
Kynurenines and other novel therapeutic strategies in the treatment of dementia
Majláth, Z., Tajti, J., & Vécsei, L. (2013) · Therapeutic Advances in Neurological Disorders · doi:10.1177/1756285613494989 · Cited by 23
“In vitro studies yielded evidence that some NSAIDs were able to decrease the level of the amyloidβ-42 peptide in cultured cells [Weggen et al., 2001], while ibuprofen treatment in an animal model of AD resulted in a reduction of the amyloid plaque load and microglial activation [Yan et al.”
BackgroundThomas, A. J., Hamilton, C. A., Donaghy, P. C., Martin-Ruiz, C. M., Morris, C. M., Barnett, N., Olsen, K., Taylor, J., & O'Brien, J. T. (2020) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.5365 · Cited by 23
Cho, H.-W., Kim, J. H., Choi, S., & Kim, H.-J. (2006) · Neuroscience Letters · doi:10.1016/j.neulet.2005.12.014 · Cited by 23
Mechanism-based treatments for Alzheimer's disease
Davies, P., & Koppel, J. L. (2009) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2009.11.2/pdavies · Cited by 23
Disposition of flurbiprofen in man: influence of stereochemistry and age
Patel, B. K., Jackson, S., Swift, C. G., & Hutt, A. J. (2003) · Xenobiotica · doi:10.1080/00498250310001602739 · Cited by 23
“NSAID use has recently been reported to be associated with a reduced risk of Alzheimer’s disease (in‘t Veld et al. 2001), which is thought to be via the suppression of b-amyloid (Ab) peptide accumulation (Weggen et al. 2001).”
BackgroundDesmethyl Derivatives of Indomethacin and Sulindac as Probes for Cyclooxygenase-Dependent Biology
Felts, A. S., Ji, C., Stafford, J. B., Crews, B. C., Kingsley, P. J., Rouzer, C. A., Washington, M. K., Subbaramaiah, K., Siegel, B. S., Young, S. M., et al. (2007) · ACS Chemical Biology · doi:10.1021/cb700077z · Cited by 23
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“Interestingly, sulindac sulfone, which is a COX-inactive oxidative metabolite of sulindac (Weggen et al., 2001), was more effective at provoking non-substrate processing than the active metabolite sulindac sulfide, but had no cytotoxic effects under conditions in which sulindac sulfide killed most…”
BackgroundInfluentialPauls, E., Bayod, S., Mateo, L., Alcalde, V., Juan-Blanco, T., Sánchez‐Soto, M., Saido, T. C., Saito, T., Berenguer, A., Attolini, C. S., et al. (2021) · Genome Medicine · doi:10.1186/s13073-021-00983-y · Cited by 23
“hypertensives as protective agents against AD [86, 87], with the potential to target the Aβ processing pathway [98].”
Anti-Inflammatory Agents and Cognitive Decline in a Bi-Racial Population
Grodstein, F., Skarupski, K. A., Bienias, J. L., Wilson, R. S., Bennett, D. A., & Evans, D. A. (2008) · Neuroepidemiology · doi:10.1159/000115749 · Cited by 23
“Noninflammatory mechanisms could be involved as well. For example, ibuprofen lowers levels of amyloid-β in the brain independent of cyclooxygenase activity, while aspirin does not have this effect [”
BackgroundStructure and modeling in the design of β‐ and γ‐secretase inhibitors
Holloway, M. K., Hunt, P. A., & McGaughey, G. B. (2009) · Drug Development Research · doi:10.1002/ddr.20291 · Cited by 22
“The concept of secretase modulation rather than inhibition was shown to be feasible by NSAIDs such as Ibuprofen [Weggen et al., 2001] and a few companies are pursuing Flurbiprofen or other arylproprionic/ acetic acid–like derivatives in/towards the clinic [Geerts, 2007; Ramsden et al., 2006].”
BackgroundAminothiazoles as γ-secretase modulators
Lübbers, T., Flohr, A., Jolidon, S., David‐Pierson, P., Jacobsen, H., Ozmen, L., & Baumann, K. (2011) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2011.08.060 · Cited by 22
Potential Use of γ-Secretase Modulators in the Treatment of Alzheimer Disease
Wagner, S. L., Tanzi, R. E., Mobley, W. C., & Galasko, D. R. (2012) · Archives of Neurology · doi:10.1001/archneurol.2012.540 · Cited by 22
Hori, T., Ishijima, J., Yokomizo, T., Ago, H., Shimizu, T., & Miyano, M. (2006) · The Journal of Biochemistry · doi:10.1093/jb/mvj176 · Cited by 22
Neurones treated with cyclo-oxygenase-1 inhibitors are resistant to amyloid-β1-42
Bate, C., Veerhuis, R., Eikelenboom, P., & Williams, A. (2003) · Neuroreport · doi:10.1097/00001756-200311140-00018 · Cited by 22
Rashid, U., & Ansari, F. L. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-803959-5.50002-7 · Cited by 23
Futai, E., Osawa, S., Cai, T., Fujisawa, T., Ishiura, S., & Tomita, T. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.629287 · Cited by 22
“In this study, we tested the effect of NSAIDs (sulindac sulfides), which modulate the cleavage reaction lowering A 42 (Table 2) (57).”
MethodA 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
“…in development include anti-Aβ immunotherapeutics, antiinflammatory, anti-angiogenic, immunomodulatory drugs, designed to decrease Aβ42 production (Weggen et al., 2001), reduce Aβ aggregation, enhance Aβ clearance from the brain, or alternatively, increase non-amyloidogenic α-secretase activity…”
BackgroundALZT-OP1: an experimental combination regimen for the treatment of Alzheimer’s disease
Lozupone, M., Berardino, G., Mollica, A., Sardone, R., Dibello, V., Zupo, R., Lampignano, L., Castellana, F., Bortone, I., Stallone, R., et al. (2022) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2022.2095261 · Cited by 22
“In fact, ibuprofen selectively lowered Aβ1-42 production in APP-transgenic mouse models of AD and in vitro [47].”
Hayden, K. M., & Welsh-Bohmer, K. A. (2011) · Current topics in behavioral neurosciences · doi:10.1007/7854_2011_152 · Cited by 31
Strömberg, K., Eketjäll, S., Georgievska, B., Tunblad, K., Eliason, K., Olsson, F., Radesäter, A., Klintenberg, R., Arvidsson, P. I., von Berg, S., et al. (2014) · FEBS Journal · doi:10.1111/febs.13103 · Cited by 23
Abdul‐Hay, S. O., Luo, J., Asghodom, R. T., & Thatcher, G. R. J. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06353.x · Cited by 21
“Flurbiprofen is also one of a subset of NSAIDs that have been reported to act as SALAs, reducing the levels of neurotoxic Ab1–42 and the ratio of Ab1–42/Ab1–40; of common NSAIDs, flurbiprofen is the most efficacious in vitro (Weggen et al. 2001; Morihara et al. 2002; Eriksen et al. 2003).”
Discovery of indole-derived pyridopyrazine-1,6-dione γ-secretase modulators that target presenilin
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Metadata
- Authors
- Weggen, S., Eriksen, J. L., Das, P., Sagi, S. A., Wang, R., Pietrzik, C. U., Findlay, K. A., Smith, T. E., Murphy, M. P., Bulter, T., Kang, D. E., Marquez-Sterling, N., Golde, T. E., & Koo, E. H.
- Affiliations
- University of California San Diego (US)
- Mayo Clinic (US)
- Icahn School of Medicine at Mount Sinai (US)
- Northwestern University (US)
- Corresponding author
- Koo, Edward H.
- ORCID
- Venue
- Nature
- Published
- 2001-11
- Volume
- 414
- Issue
- 6860
- Pages
- 212-216
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2113690827
- Cited by
- 1,388
- References
- 30
- Citations by year
- 2026: 14 · 2025: 11 · 2024: 18 · 2023: 21 · 2022: 24 · 2021: 26 · 2020: 35 · 2019: 29 · 2018: 24 · 2017: 44 · 2016: 55 · 2015: 34 · 2014: 58 · 2013: 60 · 2012: 69
- FWCI
- 53.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- 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
- nonsteroidal anti-inflammatory drugs, amyloid-beta 42, Alzheimer's disease, ibuprofen, indomethacin, cyclooxygenase-independent mechanism, amyloid precursor protein, Notch cleavage, neuroinflammation, amyloid pathology
- MeSH terms
- Alzheimer Disease, Animals, Anti-Inflammatory Agents, Non-Steroidal, Brain, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Cricetinae, Humans, Ibuprofen, Indomethacin, Mice, Transgenic, Peptide Fragments, Endopeptidases, Prostaglandin-Endoperoxide Synthases, Mass Spectrometry, Sulindac, Tumor Cells, Cultured, Amyloid beta-Peptides, Aspartic Acid Endopeptidases, CHO Cells, Amyloid beta-Protein Precursor, Mice, Amyloid Precursor Protein Secretases
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