Crude caffeine reduces memory impairment and amyloid β1–42 levels in an Alzheimer’s mouse model
Abstract
Alzheimer's disease (AD), a chronic neurodegenerative disorder associated with the abnormal accumulations of amyloid β (Aβ) peptide and oxidative stress in the brain, is the most common form of dementia among the elderly. Crude caffeine (CC), a major by-product of the decaffeination of coffee, has potent hydrophilic antioxidant activity and may reduce inflammatory processes. Here, we showed that CC and pure caffeine intake had beneficial effects in a mouse model of AD. Administration of CC or pure caffeine for 2months partially prevented memory impairment in AD mice, with CC having greater effects than pure caffeine. Furthermore, consumption of CC, but not pure caffeine, reduced the Aβ(1-42) levels and the number of amyloid plaques in the hippocampus. Moreover, CC and caffeine protected primary neurons from Aβ-induced cell death and suppressed Aβ-induced caspase-3 activity. Our data indicate that CC may contain prophylactic agents against the cell death and the memory impairment in AD.
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For some psychiatric illnesses such as Parkinson's disease, Alzheimer's disease, and depression, caffeine antagonism of adenosine receptors may improve symptoms and slow the progression of neurodegeneration, although these findings are equivocal with some studies reporting caffeine increases depressive symptoms.
“For some psychiatric illness, such as Parkinson’s disease, Alzheimer’s disease, and depression, caffeine antagonism of adenosine receptors may improve symptoms (204, 205) and slow the progression of neurodegeneration (206, 207), although these findings are equivocal with some studies reporting caffeine increases depressive symptoms (208).”
From The Safety of Ingested Caffeine: A Comprehensive Review (2017) · cites this paper as [206]
Cites
Dose translation from animal to human studies revisited.
Reagan‐Shaw, S., Nihal, M., & Ahmad, N. (2008) · The FASEB Journal · doi:10.1096/fj.07-9574lsf · Cited by 6,524 · see citing works
Pathways towards and Away from Alzheimer’s Disease
Mattson, M. P. (2004) · Nature · doi:10.1038/nature02621 · Cited by 3,052 · see citing works
Mucke, L., Masliah, E., Yu, G.-Q., Mallory, M., Rockenstein, E. M., Tatsuno, G., Hu, K., Kholodenko, D., Johnson-Wood, K., & McConlogue, L. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-11-04050.2000 · Cited by 1,856 · see citing works
Twenty years of the Alzheimer's disease amyloid hypothesis: a genetic perspective
Tanzi, R. E., & Bertram, L. (2005) · Cell · doi:10.1016/j.cell.2005.02.008 · Cited by 1,849 · see citing works
Nagahara, A. H., Merrill, D. A., Coppola, G., Tsukada, S., Schroeder, B. E., Shaked, G. M., Wang, L., Blesch, A., Kim, A., Conner, J. M., et al. (2009) · Nature Medicine · doi:10.1038/nm.1912 · Cited by 1,034 · see citing works
Apoptosis and Caspases in Neurodegenerative Diseases
Friedlander, R. M. (2003) · New England Journal of Medicine · doi:10.1056/nejmra022366 · Cited by 873 · see citing works
Arendash, G. W., Schleif, W. S., Rezai-Zadeh, K. P., Jackson, E. K., Zacharia, L. C., Cracchiolo, J. R., Shippy, D. C., & Tan, J. (2006) · Neuroscience · doi:10.1016/j.neuroscience.2006.07.021 · Cited by 459 · see citing works
Cheng, I. H.-J., Scearce-Levie, K. A., Legleiter, J. A., Palop, J. J., Gerstein, H., Bien‐Ly, N., Puolivaöli, J., Lesné, S., Ashe, K. H., Muchowski, P. J., et al. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m701078200 · Cited by 403 · see citing works
Self-citationDose‐Dependent Pharmacokinetics and Psychomotor Effects of Caffeine in Humans
Kaplan, G. B., Greenblatt, D. J., Ehrenberg, B. L., Goddard, J. E., Cotreau, M. M., Harmatz, J. S., & Shader, R. I. (1997) · The Journal of Clinical Pharmacology · doi:10.1002/j.1552-4604.1997.tb04356.x · Cited by 387 · see citing works
Canas, P. M., Porciúncula, L. O., Cunha, G. M. A., Silva, C. G., Machado, N. J., Oliveira, J. M. A., Oliveira, C. R., & Cunha, R. A. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.3728-09.2009 · Cited by 358 · see citing works
The neuroprotective effects of caffeine: A prospective population study (the Three City Study)
Ritchie, K., Carrière, I., de Mendonça, A., Portet, F., Dartigues, J. F., Rouaud, O., Barberger-Gateau, P., & Ancelin, M. L. (2007) · Neurology · doi:10.1212/01.wnl.0000266670.35219.0c · Cited by 347 · see citing works
Nitration of Tyrosine 10 Critically Enhances Amyloid β Aggregation and Plaque Formation
Kummer, M. P., Hermes, M., Delekarte, A., Hammerschmidt, T., Kumar, S., Terwel, D., Walter, J., Pape, H.-C., König, S., Roeber, S., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.07.001 · Cited by 336 · see citing works
Arendash, G. W., Mori, T., Cao, C., Mamcarz, M., Runfeldt, M., Dickson, A., Rezai-Zadeh, K., Tan, J., Citron, B. A., Lin, X., et al. (2009) · Journal of Alzheimer s Disease · doi:10.3233/jad-2009-1087 · Cited by 308 · see citing works
Butterfield, D. A., & Debra Boyd-kimball, A. (2004) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2004.10.014 · Cited by 267 · see citing works
Cunha, R. A., & Agostinho, P. M. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-1408 · Cited by 233 · see citing works
Oxidative imbalance in patients with mild cognitive impairment and Alzheimer’s disease
GUIDI, I., GALIMBERTI, D., LONATI, S., NOVEMBRINO, C., BAMONTI, F., TIRITICCO, M., FENOGLIO, C., VENTURELLI, E., BARON, P., & BRESOLIN, N. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.01.001 · Cited by 203 · see citing works
Nonsteroidal anti-inflammatory drugs lower Aβ42 and change presenilin 1 conformation
Lleó, A., Berezovska, O., Herl, L. D., Raju, S., Deng, A., Bacskai, B. J., Frosch, M. P., Irizarry, M. C., & Hyman, B. T. (2004) · Nature Medicine · doi:10.1038/nm1112 · Cited by 198 · see citing works
Prasanthi, J. R. P., Dasari, B., Marwarha, G., Larson, T., Chen, X., Geiger, J. D., & Ghribi, O. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2010.07.007 · Cited by 159 · see citing works
Alhaider, I. A., Aleisa, A. M., Tran, T. T., Alzoubi, K. H., & Alkadhi, K. A. (2010) · SLEEP · doi:10.1093/sleep/33.4.437 · Cited by 151 · see citing works
Duarte, J. M. N., Carvalho, R. A., Cunha, R. A., & Rolf Gruetter, A. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06349.x · Cited by 140 · see citing works
da Costa, M. S., Botton, P. H. S., Mioranzza, S., Ardais, A. P., Moreira, J. D., Souza, D. O., & Porciúncula, L. O. (2008) · Neurochemistry International · doi:10.1016/j.neuint.2008.06.006 · Cited by 106 · see citing works
Caffeine reverses the memory disruption induced by intra-nigral MPTP-injection in rats
Gevaerd, M. S., Takahashi, R. N., Silveira, R., & Cunha, C. D. (2001) · Brain Research Bulletin · doi:10.1016/s0361-9230(01)00501-9 · Cited by 104 · see citing works
Caffeine, cognitive failures and health in a non‐working community sample
Smith, A. P. (2009) · Human Psychopharmacology: Clinical and Experimental · doi:10.1002/hup.991 · Cited by 102 · see citing works
Effects of caffeine and glucose, alone and combined, on cognitive performance
Adan, A., & Serra-Grabulosa, J. M. (2010) · Human psychopharmacology · doi:10.1002/hup.1115 · Cited by 100 · see citing works
Alcohol-induced retrograde memory impairment in rats: prevention by caffeine
Spinetta, M. J., Woodlee, M. T., Feinberg, L. M., Stroud, C., Schallert, K., Cormack, L. K., & Schallert, T. J. (2008) · Psychopharmacology · doi:10.1007/s00213-008-1294-5 · Cited by 96 · see citing works
Chu, Y.-F., Brown, P. H., Lyle, B. J., Chen, Y., Black, R. M., Williams, C. E., Lin, Y.-C., Hsu, C.-W., & Cheng, I. H. (2009) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf902095z · Cited by 89 · see citing works
Self-citationEffect of caffeine on self‐sustained firing in human motor units
Walton, C., Kalmar, J. M., & CAFARELLI, E. (2002) · The Journal of Physiology · doi:10.1113/jphysiol.2002.025064 · Cited by 84 · see citing works
Alhaider, I. A., Aleisa, A. M., Tran, T. T., & Alkadhi, K. A. (2010) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2010.07175.x · Cited by 84 · see citing works
Cao, C., Wang, L., Lin, X., Mamcarz, M. B., Zhang, C., Bai, G., Nong, J., Sussman, S., & Arendash, G. W. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-110110 · Cited by 75 · see citing works
Chu, Y.-F., Chen, Y., Black, R. M., Brown, P. H., Lyle, B. J., Liu, R. H., & Ou, B. (2011) · Food Chemistry · doi:10.1016/j.foodchem.2010.07.019 · Cited by 55 · see citing works
Self-citationHagen, K., Thoresen, K., Stovner, L. J., & Zwart, J. (2009) · The Journal of Headache and Pain · doi:10.1007/s10194-009-0114-6 · Cited by 50 · see citing works
Biomarkers of inflammation and amyloid-β phagocytosis in patients at risk of Alzheimer disease
Fiala, M., & Veerhuis, R. (2009) · Experimental Gerontology · doi:10.1016/j.exger.2009.08.003 · Cited by 45 · see citing works
Chu, Y., Chen, Y., Brown, P. H., Lyle, B. J., Black, R. M., Cheng, I. H.-J., Ou, B., & Prior, R. L. (2011) · Food Chemistry · doi:10.1016/j.foodchem.2011.09.024 · Cited by 38 · see citing works
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Cappelletti, S., Daria, P., Sani, G., & Aromatario, M. (2015) · Current Neuropharmacology · doi:10.2174/1570159x13666141210215655 · Cited by 631 · see citing works
The Safety of Ingested Caffeine: A Comprehensive Review
Temple, J. L., Bernard, C., Lipshultz, S. E., Czachor, J. D., Westphal, J. A., & Mestre, M. A. (2017) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2017.00080 · Cited by 557 · see citing works
The amyloid cascade-inflammatory hypothesis of Alzheimer disease: implications for therapy
McGeer, P. L., & McGeer, E. G. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1177-7 · Cited by 467 · see citing works
Driscoll, I., Shumaker, S. A., Snively, B. M., Margolis, K. L., Manson, J. E., Vitolins, M. Z., Rossom, R. C., & Espeland, M. A. (2016) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glw078 · Cited by 55 · see citing works
Fukuyama, K., Kakio, S., Nakazawa, Y., Kobata, K., Funakoshi‐Tago, M., Suzuki, T., & Tamura, H. (2018) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201800238 · Cited by 22 · see citing works
Khezri, M. R., & Ghasemnejad-Berenji, M. (2023) · Journal of Alzheimer s Disease · doi:10.3233/jad-220873 · Cited by 12 · see citing works
- Authors
- Chu, Y.-F., Chang, W.-H., Black, R. M., Liu, J.-R., Sompol, P., Chen, Y., Wei, H., Zhao, Q., & Cheng, I. H.
- Affiliations
- National Yang Ming University (TW)
- Boston Children's Hospital (US)
- University of Kentucky (US)
- Corresponding author
- Cheng, Irene H.
- Venue
- Food Chemistry
- Publisher
- Elsevier BV
- Published
- 2012-12
- Volume
- 135
- Issue
- 3
- Pages
- 2095-2102
- ISSN
- 0308-8146 (ISSN-L)
- OpenAlex
- W2101121942
- Cited by
- 106
- References
- 33
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 6 · 2023: 2 · 2022: 12 · 2021: 8 · 2020: 7 · 2019: 10 · 2018: 14 · 2017: 9 · 2016: 6 · 2015: 9 · 2014: 13 · 2013: 5 · 2012: 2
- FWCI
- 6.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Food Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Health Research Institutes (NHRI-EX100-9816NC)
- Taiwan National Science Council (NSC97-2320-B-010-027-MY3)
- Taiwan Ministry of Education Aim for Top University
- Kraft Foods Global, Inc.
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- caffeine, Alzheimer's disease, amyloid-beta 42, memory impairment, amyloid plaques, hippocampus, oxidative stress, antioxidant activity, neuroprotection, caspase-3, neurodegeneration
- MeSH terms
- Alzheimer Disease, Animals, Caffeine, Disease Models, Animal, Humans, Male, Memory, Mice, Inbred C57BL, Mice, Transgenic, Plant Extracts, Amyloid beta-Peptides, Maze Learning, Coffea, Mice, Caspase 3
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