Cited by 1,388Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

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A subset of NSAIDs lower amyloidogenic Aβ42 independently of cyclooxygenase activity

Weggen, Sascha, Eriksen, Jason L., Das, Pritam, Sagi, Sarah A., Wang, Rong, Pietrzik, Claus U., Findlay, Kirk A., Smith, Tawnya E., Murphy, Michael P., Bulter, Thomas, Kang, David E., Marquez-Sterling, Numa, Golde, Todd E., Koo, Edward H.·2001·Nature

DOI 10.1038/35102591

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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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“Ibuprofen treatment of Tg2576 transgenic mice Female Tg2576 mice overexpressing APP695 containing the ‘Swedish’ mutation were treated at 3 months old, when they show high levels of soluble Aβ in brain but no signs of Aβ depositio”
Background
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Moore, B. D., Martin, J., de Mena, L., Sánchez, J., Cruz, P. E., Ceballos‐Diaz, C., Ladd, T. B., Ran, Y., Levites, Y., Kukar, T. L., et al. (2017) · The Journal of Experimental Medicine · doi:10.1084/jem.20170600 · Cited by 89
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“A different modifier of γ-secretase specifically acting on APP but not on Notch cleavage is the non-steroid anti-inflammatory drug (NSAID) Sulindac sulfide [124, 125].”
Background
A Molecular Mechanism for Ibuprofen-Mediated RhoA Inhibition in Neurons
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“…NSAIDs, including ibuprofen, have been shown to reduce the risk of Alzheimer’s disease via the mechanisms independent of cyclooxygenase inhibition (Weggen et al., 2001), although clinical trials with some NSAIDs did not show beneficial effects for Alzheimer’s disease patients (de Jong et al.,…”
Background
Validation of amyloid-β peptides in CSF diagnosis of neurodegenerative dementias
Bibl, M., Mollenhauer, B., Lewczuk, P., Esselmann, H., Wolf, S., Trenkwalder, C., Otto, M., Stiens, G., Rüther, E., Kornhuber, J., et al. (2007) · Molecular Psychiatry · doi:10.1038/sj.mp.4001967 · Cited by 93
Nitrous oxide analgesia for minor pediatric surgical procedures: an effective alternative to conscious sedation?
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“lowering GSMs are of therapeutic interests and the “signature” of these compounds is that they decrease Aβ42 production and increase Aβ peptides shorter than Aβ1–40 (Weggen et al., 2001).”
Self-citation
Novel γ-Secretase Enzyme Modulators Directly Target Presenilin Protein
Ebke, A., Luebbers, T., Fukumori, A., Shirotani, K., Haass, C., Baumann, K., & Steiner, H. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.c111.276972 · Cited by 88
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“Another study by Weggen et al found that COX-2 inhibition reduced the production of A b 42 and the formation of amyloid plaques in the hippocampus of transgenic mice (Weggen et al., 2001).”
Multifunctional drugs with different CNS targets for neuropsychiatric disorders
der Schyf, C. J. V., Geldenhuys, W. J., & Youdim, M. B. H. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04141.x · Cited by 88
“secretion of amyloidogenic Ab42 in cultured cells of an AD model (Weggen et al. 2001).”
Background
Emerging Therapeutics for Alzheimer's Disease
Chiang, K., & Koo, E. H. (2014) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-011613-135932 · Cited by 95
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“Nonsteroidal anti-inflammatory drugs (NSAID’s) have been identified as prototypic agents capable of lowering beta amyloid both in vitro and in vivo (Weggen et al., 2001; Eriksen et al., 2003).”
Background
Medicinal chemistry approaches for the treatment and prevention of Alzheimer's disease
Бачурин, С. О. (2002) · Medicinal Research Reviews · doi:10.1002/med.10026 · Cited by 91
Back to the future: the 'old-fashioned' way to new medications for neurodegeneration
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Lao, K., Ji, N., Zhang, X., Qiao, W., Tang, Z., & Gou, X. (2019) · Journal of drug targeting · doi:10.1080/1061186x.2018.1474361 · Cited by 86
“a safer alternative to GSIs for the reduction of toxic Ab42 in the treatment of AD [40] (Figure 4).”
Background
Statins reduce the neurofibrillary tangle burden in a mouse model of tauopathy
Boimel, M., Grigoriadis, N., Lourbopoulos, A., Touloumi, O., Rosenmann, D., Abramsky, O., & Rosenmann, H. (2009) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e31819ac3cb · Cited by 86
CHF5074, a novel γ‐secretase modulator, attenuates brain β‐amyloid pathology and learning deficit in a mouse model of Alzheimer's disease
Imbimbo, B. P., Hutter‐Paier, B., Villetti, G., Facchinetti, F., Cenacchi, V., Volta, R., Lanzillotta, A., Pizzi, M., & Windisch, M. (2009) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2008.00097.x · Cited by 87
Non-Steroidal Anti-Inflammatory Drugs in Alzheimer's Disease and Parkinson's Disease: Reconsidering the Role of Neuroinflammation
Moore, A. H., Bigbee, M. J., Boynton, G. E., Wakeham, C. M., Rosenheim, H. M., Staral, C. J., Morrissey, J. L., & Hund, A. K. (2010) · Pharmaceuticals · doi:10.3390/ph3061812 · Cited by 90
The Novel γ Secretase Inhibitor N-[cis-4-[(4-Chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)cyclohexyl]-1,1,1-trifluoromethanesulfonamide (MRK-560) Reduces Amyloid Plaque Deposition without Evidence of Notch-Related Pathology in the Tg2576 Mouse
Best, J. D., Smith, D. W., Reilly, M., O’Donnell, R., Lewis, H. D., Ellis, S., Wilkie, N., Rosahl, T. W., Laroque, P. A., Boussiquet-Leroux, C., et al. (2006) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.106.114330 · Cited by 84
“Such compounds include a subset of NSAIDs, which preferentially reduced A (42) production without seeming to affect A (40) or Notch processing (Weggen et al., 2001, 2003).”
Background
Quantum Chemical and Docking Insights into Bioavailability Enhancement of Curcumin by Piperine in Pepper
Patil, V. M., Das, S., & Balasubramanian, K. (2016) · The Journal of Physical Chemistry A · doi:10.1021/acs.jpca.6b01434 · Cited by 85
Disease-Modifying Approach to the Treatment of Alzheimerʼs Disease
Panza, F., Solfrizzi, V., Frisardi, V., Capurso, C. A., D’Introno, A., Colacicco, A. M., Vendemiale, G., Capurso, A., & Imbimbo, B. P. (2009) · Drugs & Aging · doi:10.2165/11315770-000000000-00000 · Cited by 87
“g-Secretasemodulation was first observed in 2001 with certain NSAIDs that were capable of altering the cleavage properties of g-secretase to lower the production of Ab42, both in cultured cells and in transgenic mouse models, and increase the formation of a shorter 38-residue species (Ab38);([118,119]) these NSAIDs in…”
Oxidative Stress, Mitochondrial Abnormalities and Proteins Deposition: Multitarget Approaches in Alzheimer's Disease
Giulia, N., Sestito, S., Digiacomo, M., & Rapposelli, S. (2017) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026617666170607114232 · Cited by 86
Localization and Trafficking of Amyloid-β Protein Precursor and Secretases: Impact on Alzheimer's Disease
Agostinho, P. M., Pliássova, A., Oliveira, C. R., & Cunha, R. A. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-142730 · Cited by 90
“Some of nonsteroidal anti-inflammatory drugs, such as ibuprofen, indomethacin, and sulindac sulfide, act as -secretase modulators that cause a decrease in the formation of A 42 and concomitant increase in shorter A species, mainly A 38 [159, 160].”
Background
Patient-Administered Nitrous Oxide/Oxygen Inhalation Provides Safe and Effective Analgesia for Percutaneous Liver Biopsy: A Randomized Placebo-Controlled Trial
Castéra, L., Nègre, I., Samii, K., & Buffet, C. (2001) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2001.03776.x · Cited by 84
Protective effects of antioxidants and anti-inflammatory agents against manganese-induced oxidative damage and neuronal injury
Milatović, D., Gupta, R. C., Yu, Y., Zaja‐Milatovic, S., & Aschner, M. (2011) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2011.06.001 · Cited by 85
“Next, we tested the efficacy of ibuprofen, a NSAID with some COX-independent actions (Asanuma et al., 2001; Weggen et al., 2001), in attenuating the Mn-induced effects.”
Method
γ-Secretase in biology and medicine
Wolfe, M. S. (2009) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2008.12.011 · Cited by 85
1-(3′,4′-Dichloro-2-fluoro[1,1′-biphenyl]-4-yl)-cyclopropanecarboxylic Acid (CHF5074), a Novel γ-Secretase Modulator, Reduces Brain β-Amyloid Pathology in a Transgenic Mouse Model of Alzheimer’s Disease without Causing Peripheral Toxicity
Imbimbo, B. P., Giudice, E. D., Colavito, D., D’Arrigo, A., Carbonare, M. D., Villetti, G., Facchinetti, F., Volta, R., Pietrini, V., Baroc, M. F., et al. (2007) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.107.129007 · Cited by 84
“not inhibit the γ-secretase-mediated cleavages of either APP at the alternative ε site, or Notch-1 at the S3 site (Weggen et al., 2001; Weggen et al., 2003b).”
BackgroundInfluential
Mechanisms of Action of Non-Steroidal Anti-Inflammatory Drugs for the Prevention of Alzheimers Disease
Cole, G. M., & Frautschy, S. A. (2010) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/187152710791011991 · Cited by 85
“[10] demonstrated that a selective subset of NSAIDs, including ibuprofen and indomethacin (but not naproxen), can reduce γ-secretase production of amyloid β-peptide (1–42) (Aβ42).”
Background
Does neuroinflammation drive the relationship between tau hyperphosphorylation and dementia development following traumatic brain injury?
Collins-Praino, L. E., & Corrigan, F. (2017) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2016.09.027 · Cited by 95
“…that the effect of NSAIDs was predominantly due to the role that NSAIDs have on c-secretase modulation, which reduce levels of Ab production (Weggen et al., 2001) However, a follow-up study utilizing the R-flurbiprofen, (Morihara et al., 2002) found that a 2 month period of treatment in…”
Background
Multifunctional role of zinc in human health: an update
Kiouri, D. P., Tsoupra, E., Peana, M., Perlepes, S. P., Stefanidou, M. E., & Chasapis, C. T. (2023) · EXCLI journal · doi:10.17179/excli2023-6335 · Cited by 102
“Experiments have shown that the NSAIDs ibuprofen and sulindac decrease the levels of longer Aβ forms (mainly Aβ1-42), with corresponding increase in shorter isoforms (Weggen et al., 2001).”
Background
Generation of C‐terminally truncated amyloid‐β peptides is dependent on γ‐secretase activity
Beher, D., Wrigley, J. D. J., Owens, A. P., & Shearman, M. S. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.00985.x · Cited by 84
“2002 International Society for Neurochemistry, Journal of Neurochemistry, 82, 563–575 (NSAIDS) can selectively lower Ab(1–42) and correspondingly increase the production of Ab(1–38) (Weggen et al. 2001)11 .”
Background
γ-Secretase as a Target for Alzheimer’s Disease
Wolfe, M. S. (2012) · Advances in pharmacology · doi:10.1016/b978-0-12-394816-8.00004-0 · Cited by 85
Modulation of γ-secretase specificity using small molecule allosteric inhibitors
Shelton, C. C., Zhu, L., Chau, D.-M., Yang, L., Wang, R., Djaballah, H., Zheng, H., & Li, Y. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0910757106 · Cited by 82
“Additionally, we determined that both lead compounds did not promote A 38 production, which is distinct from the previously reported GSMs (12).”
BackgroundResultInfluentialSelf-citation
Potential Therapeutic Strategies for Alzheimer’s Disease Targeting or Beyondβ-Amyloid: Insights from Clinical Trials
Jia, Q., Deng, Y., & Qing, H. (2014) · BioMed Research International · doi:10.1155/2014/837157 · Cited by 84
“Here we attempt to summarize and compare putative therapeutic strategies that have completed clinical trials or are currently being tested from various perspectives to provide insights for treatments of Alzheimer’s disease.”
Background
Role of peroxisome proliferator-activated receptor γ in amyloid precursor protein processing and amyloid β-mediated cell death
d’Abramo, C., Massone, S., Zingg, J.-M., Pizzuti, A., Marambaud, P., Piccola, B. D., Azzi, A., Marinari, U. M., Pronzato, M. A., & Ricciarelli, R. (2005) · Biochemical Journal · doi:10.1042/bj20050560 · Cited by 81
High mobility group box protein‐1 inhibits microglial Aβ clearance and enhances Aβ neurotoxicity
Takata, K., Kitamura, Y., Tsuchiya, D., Kawasaki, T., Taniguchi, T., & Shimohama, S. (2004) · Journal of Neuroscience Research · doi:10.1002/jnr.20340 · Cited by 82
“, 2001), a recent study reported that these drugs may lower the production of A 42 independently of the inhibition of cyclooxygenase, an inflammatory mediator (Weggen et al., 2001).”
Background
C-Terminal Turn Stability Determines Assembly Differences between Aβ40 and Aβ42
Roychaudhuri, R., Yang, M., Deshpande, A. M., Cole, G. M., Frautschy, S. A., Lomakin, A., Benedek, G. B., & Teplow, D. B. (2012) · Journal of Molecular Biology · doi:10.1016/j.jmb.2012.11.006 · Cited by 82
“All rights reserve distinguished by the absence or presence, respectively, of an Ile–Ala dipeptide at the C-terminal end of an identical 40-amino-acid peptide.4 Aβ42 is the principal protein component of parenchymal plaques.5–7 An increase in the absolute amount of Aβ42, or in the Aβ42/Aβ40 concentration ratio, is ass…”
Background
Anti-amyloidogenic therapies: strategies for prevention and treatment of Alzheimer’s disease
Hamaguchi, T., Ono, K., & Yamada, M. (2006) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-005-5599-9 · Cited by 83
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Background
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“Also, these trials may not have addressed the right molecular targets (cf., e.g., Weggen et al., 2001).”
Background
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McGeer, P. L., & McGeer, E. G. (2002) · Trends in Molecular Medicine · doi:10.1016/s1471-4914(02)02422-x · Cited by 80
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“NSAID differs by pharmacokinetics and pharmacodynamics profiles, including NSAID concentration reaching the brain and COX-2-specific molecular targets, and only a subset of NSAIDs can lower Aβ production [72,73].”
Background
A potential nitrergic mechanism of action for indomethacin, but not of other COX inhibitors: relevance to indomethacin-sensitive headaches
Summ, O., Andreou, A. P., Akerman, S., & Goadsby, P. J. (2010) · The Journal of Headache and Pain · doi:10.1007/s10194-010-0263-7 · Cited by 79
“A mechanism where no direct correlation to the COX inhibitory effect of the NSAIDs can be seen was uncovered after the observation has been made that long term medication with NSAIDs can lower the risk for development Alzheimer’s disease [40].”
Background
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Sereniki, A., & Vital, M. A. B. F. (2008) · Revista de Psiquiatria do Rio Grande do Sul · doi:10.1590/s0101-81082008000200002 · Cited by 121
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“One recent study showed that, in transfected cells and mutant APP transgenic mice, some NSAIDs actually decreased production of A 42 and, quite surprisingly, led to an increase in A 38, suggesting that active NSAIDs exert a novel effect on -secretase activity (Weggen et al., 2001).”
Background
Characterizations of distinct amyloidogenic conformations of the Aβ (1–40) and (1–42) peptides
Lim, K. H., Collver, H. H., Le, Y. T. H., Nagchowdhuri, P. S., & Kenney, J. M. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.12.043 · Cited by 80
The 28‐amino acid form of an APLP1‐derived Aβ‐like peptide is a surrogate marker for Aβ42 production in the central nervous system
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“Although sulindac sulﬁde (Weggen et al, 2001) and compound-W (Okochi et al, 2006) have been shown to lower the relative A b 42 level to total A b , they did not cause a decrease in the relative APL1 b 28 level to total APL1 b (see Fig S7B–”
PPARs in Alzheimer′s Disease
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“It has also been suggested that NSAIDs act directly on Aβ processing by the γ-secretase complex resulting in selective decrease of Aβ42 production [56, 57], even so this hypothesis has recently been challenged [58, 59].”
Background
Potential role of the formyl peptide receptor-like 1 (FPRL1) in inflammatory aspects of Alzheimer's disease
Cui, Y., Le, Y., Yazawa, H., Gong, W., & Wang, J. M. (2002) · Journal of Leukocyte Biology · doi:10.1189/jlb.72.4.628 · Cited by 79
“One of the NSAIDs, ibuprofen, significantly reduces the proinflammatory responses in brains of the murine AD model and may directly inhibit the aberrant production of A42 by neuronal cells [ 84 ].”
Background
Two diseases, one approach: multitarget drug discovery in Alzheimer's and neglected tropical diseases
Prati, F., Uliassi, E., & Bolognesi, M. L. (2014) · MedChemComm · doi:10.1039/c4md00069b · Cited by 77
A randomised, controlled, crossover trial of oral midazolam and nitrous oxide for paediatric dental sedation
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“Ibuprofen (Lim et al. 2001; Weggen et al. 2001, 2003; Zhou et al. 2003), indomethacin and suldinac sulfide lower Aβ42, whereas NSAIDs without significant Rho-inhibiting properties are not effective.”
Interleukin-6, β-amyloid peptide and NMDA interactions in rat cortical neurons
Qiu, Z., & Gruol, D. L. (2003) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(03)00158-9 · Cited by 79
The Non-cyclooxygenase Targets of Non-steroidal Anti-inflammatory Drugs, Lipoxygenases, Peroxisome Proliferator-activated Receptor, Inhibitor of κB Kinase, and NFκB, Do Not Reduce Amyloid β42 Production
Sagi, S. A., Weggen, S., Eriksen, J. L., Golde, T. E., & Koo, E. H. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m303588200 · Cited by 76
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Anti-amyloid-β protein agents for the treatment of Alzheimer’s disease: an update on emerging drugs
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“[17] reported that the group of NSAIDs shifted the c-secretase cleavage site on APP from the Ab42 position to Ab38, selectively reducing Ab42 generation.”
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Structural Association of Nonsteroidal Anti-Inflammatory Drugs with Lipid Membranes
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The Backbone Dynamics of the Amyloid Precursor Protein Transmembrane Helix Provides a Rationale for the Sequential Cleavage Mechanism of γ-Secretase
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Syntheses of (−)-Oleocanthal, a Natural NSAID Found in Extra Virgin Olive Oil, the (−)-Deacetoxy-Oleuropein Aglycone, and Related Analogues
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Mild cholesterol depletion reduces amyloid‐β production by impairing APP trafficking to the cell surface
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Integrated communications between cyclooxygenase‐2 and Alzheimer's disease
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“One typical category of GSMs is NSAIDs (non-steroid antiinflammatory drug), including ibuprofen, sulindac sulfide, and indomethacin, which selectively lower Aβ42 without affecting NICD generation [9].”
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Therapeutic implications of the prostaglandin pathway in Alzheimer's disease
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“Second, some of, but not all NSAIDs directly affect amyloid pathology in the brain by altering -secretase activity and reducing -amyloid peptide levels independently of COX activity (48).”
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γ-Secretase Inhibition and Modulation for Alzheimers Disease
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BackgroundMethodResultInfluential
The metalloprotease ADAMTS4 generates N-truncated Aβ4–x species and marks oligodendrocytes as a source of amyloidogenic peptides in Alzheimer’s disease
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“Of note, the very first GSMs were NSAIDs, whose effect on increasing Ab38 while reducing Ab42 production was first discovered thorough a phenotypic screen in transfected cells and ascribed to a mechanism independent of their previously knownmolecular targets (Weggen et al., 2001).”
Background
Novel Anti-Alzheimer’s Therapeutic Molecules Targeting Amyloid Precursor Protein Processing
Uddin, M. S., Kabir, M. T., Jeandet, P., Mathew, B., Ashraf, G. M., Perveen, A., Bin-Jumah, M. N., Mousa, S. A., & Abdel‐Daim, M. M. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/7039138 · Cited by 67
“This study reported a decreased prevalence of AD among the individuals who were administered nonsteroidal antiinflammatory drugs (NSAIDs) [138].”
BackgroundInfluential

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: Weggen, Sascha
Eriksen, Jason L.
Das, Pritam
Wang, Rong
Pietrzik, Claus U.
Kang, David E.
Golde, Todd E.
Koo, Edward H.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2001-11
Volume: 414
Issue: 6860
Pages: 212-216
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/35102591
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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A subset of NSAIDs lower amyloidogenic Aβ42 independently of cyclooxygenase activity

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