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Caffeine protects Alzheimer's mice against cognitive impairment and reduces brain beta-amyloid production.
Neuroscience. 2006 Nov 03; 142(4):941-52.N

Abstract

A recent epidemiological study suggested that higher caffeine intake over decades reduces the risk of Alzheimer's disease (AD). The present study sought to determine any long-term protective effects of dietary caffeine intake in a controlled longitudinal study involving AD transgenic mice. Caffeine (an adenosine receptor antagonist) was added to the drinking water of amyloid precursor protein, Swedish mutation (APPsw) transgenic (Tg) mice between 4 and 9 months of age, with behavioral testing done during the final 6 weeks of treatment. The average daily intake of caffeine per mouse (1.5 mg) was the human equivalent of 500 mg caffeine, the amount typically found in five cups of coffee per day. Across multiple cognitive tasks of spatial learning/reference memory, working memory, and recognition/identification, Tg mice given caffeine performed significantly better than Tg control mice and similar to non-transgenic controls. In both behaviorally-tested and aged Tg mice, long-term caffeine administration resulted in lower hippocampal beta-amyloid (Abeta) levels. Expression of both Presenilin 1 (PS1) and beta-secretase (BACE) was reduced in caffeine-treated Tg mice, indicating decreased Abeta production as a likely mechanism of caffeine's cognitive protection. The ability of caffeine to reduce Abeta production was confirmed in SweAPP N2a neuronal cultures, wherein concentration-dependent decreases in both Abeta1-40 and Abeta1-42 were observed. Although adenosine A(1) or A(2A) receptor densities in cortex or hippocampus were not affected by caffeine treatment, brain adenosine levels in Tg mice were restored back to normal by dietary caffeine and could be involved in the cognitive protection provided by caffeine. Our data demonstrate that moderate daily intake of caffeine may delay or reduce the risk of AD.

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Authors+Show Affiliations

Arendash GW
The Byrd Alzheimer's Center and Research Institute, Tampa, FL 33647, USA. arendash@cas.usf.edu
Schleif W
No affiliation info available
Rezai-Zadeh K
No affiliation info available
Jackson EK
No affiliation info available
Zacharia LC
No affiliation info available
Cracchiolo JR
No affiliation info available
Shippy D
No affiliation info available
Tan J
No affiliation info available

MeSH

AdenosineAlzheimer DiseaseAmyloid Precursor Protein SecretasesAmyloid beta-PeptidesAnimalsBrainCaffeineCell Line, TumorCognition DisordersDisease Models, AnimalDose-Response Relationship, DrugMemory DisordersMemory, Short-TermMiceMice, Inbred C57BLMice, TransgenicNeuroprotective AgentsNeuropsychological TestsPeptide FragmentsPresenilin-1Purinergic P1 Receptor AntagonistsReceptors, Purinergic P1Treatment Outcome

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16938404

Citation

Arendash, G W., et al. "Caffeine Protects Alzheimer's Mice Against Cognitive Impairment and Reduces Brain Beta-amyloid Production." Neuroscience, vol. 142, no. 4, 2006, pp. 941-52.
Arendash GW, Schleif W, Rezai-Zadeh K, et al. Caffeine protects Alzheimer's mice against cognitive impairment and reduces brain beta-amyloid production. Neuroscience. 2006;142(4):941-52.
Arendash, G. W., Schleif, W., Rezai-Zadeh, K., Jackson, E. K., Zacharia, L. C., Cracchiolo, J. R., Shippy, D., & Tan, J. (2006). Caffeine protects Alzheimer's mice against cognitive impairment and reduces brain beta-amyloid production. Neuroscience, 142(4), 941-52.
Arendash GW, et al. Caffeine Protects Alzheimer's Mice Against Cognitive Impairment and Reduces Brain Beta-amyloid Production. Neuroscience. 2006 Nov 3;142(4):941-52. PubMed PMID: 16938404.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Caffeine protects Alzheimer's mice against cognitive impairment and reduces brain beta-amyloid production. AU - Arendash,G W, AU - Schleif,W, AU - Rezai-Zadeh,K, AU - Jackson,E K, AU - Zacharia,L C, AU - Cracchiolo,J R, AU - Shippy,D, AU - Tan,J, Y1 - 2006/08/28/ PY - 2006/05/22/received PY - 2006/06/27/revised PY - 2006/07/11/accepted PY - 2006/8/30/pubmed PY - 2007/2/28/medline PY - 2006/8/30/entrez SP - 941 EP - 52 JF - Neuroscience JO - Neuroscience VL - 142 IS - 4 N2 - A recent epidemiological study suggested that higher caffeine intake over decades reduces the risk of Alzheimer's disease (AD). The present study sought to determine any long-term protective effects of dietary caffeine intake in a controlled longitudinal study involving AD transgenic mice. Caffeine (an adenosine receptor antagonist) was added to the drinking water of amyloid precursor protein, Swedish mutation (APPsw) transgenic (Tg) mice between 4 and 9 months of age, with behavioral testing done during the final 6 weeks of treatment. The average daily intake of caffeine per mouse (1.5 mg) was the human equivalent of 500 mg caffeine, the amount typically found in five cups of coffee per day. Across multiple cognitive tasks of spatial learning/reference memory, working memory, and recognition/identification, Tg mice given caffeine performed significantly better than Tg control mice and similar to non-transgenic controls. In both behaviorally-tested and aged Tg mice, long-term caffeine administration resulted in lower hippocampal beta-amyloid (Abeta) levels. Expression of both Presenilin 1 (PS1) and beta-secretase (BACE) was reduced in caffeine-treated Tg mice, indicating decreased Abeta production as a likely mechanism of caffeine's cognitive protection. The ability of caffeine to reduce Abeta production was confirmed in SweAPP N2a neuronal cultures, wherein concentration-dependent decreases in both Abeta1-40 and Abeta1-42 were observed. Although adenosine A(1) or A(2A) receptor densities in cortex or hippocampus were not affected by caffeine treatment, brain adenosine levels in Tg mice were restored back to normal by dietary caffeine and could be involved in the cognitive protection provided by caffeine. Our data demonstrate that moderate daily intake of caffeine may delay or reduce the risk of AD. SN - 0306-4522 UR - https://www.unboundmedicine.com/medline/citation/16938404/Caffeine_protects_Alzheimer's_mice_against_cognitive_impairment_and_reduces_brain_beta_amyloid_production_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(06)00937-7 DB - PRIME DP - Unbound Medicine ER -