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Caffeine reverses cognitive impairment and decreases brain amyloid-beta levels in aged Alzheimer's disease mice.
J Alzheimers Dis. 2009; 17(3):661-80.JA

Abstract

We have recently shown that Alzheimer's disease (AD) transgenic mice given a moderate level of caffeine intake (the human equivalent of 5 cups of coffee per day) are protected from development of otherwise certain cognitive impairment and have decreased hippocampal amyloid-beta (Abeta) levels due to suppression of both beta-secretase (BACE1) and presenilin 1 (PS1)/gamma-secretase expression. To determine if caffeine intake can have beneficial effects in "aged" APPsw mice already demonstrating cognitive impairment, we administered caffeine in the drinking water of 18-19 month old APPsw mice that were impaired in working memory. At 4-5 weeks into caffeine treatment, those impaired transgenic mice given caffeine (Tg/Caff) exhibited vastly superior working memory compared to the continuing impairment of control transgenic mice. In addition, Tg/Caff mice had substantially reduced Abeta deposition in hippocampus (decrease 40%) and entorhinal cortex (decrease 46%), as well as correlated decreases in brain soluble Abeta levels. Mechanistically, evidence is provided that caffeine suppression of BACE1 involves the cRaf-1/NFkappaB pathway. We also determined that caffeine concentrations within human physiological range effectively reduce active and total glycogen synthase kinase 3 levels in SweAPP N2a cells. Even with pre-existing and substantial Abeta burden, aged APPsw mice exhibited memory restoration and reversal of AD pathology, suggesting a treatment potential of caffeine in cases of established AD.

Authors+Show Affiliations

Department of Cell Biology, Florida Alzheimer's Disease Research Center, University of South Florida, Tampa, FL 33620, USA. arendash@cas.usf.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19581722

Citation

Arendash, Gary W., et al. "Caffeine Reverses Cognitive Impairment and Decreases Brain Amyloid-beta Levels in Aged Alzheimer's Disease Mice." Journal of Alzheimer's Disease : JAD, vol. 17, no. 3, 2009, pp. 661-80.
Arendash GW, Mori T, Cao C, et al. Caffeine reverses cognitive impairment and decreases brain amyloid-beta levels in aged Alzheimer's disease mice. J Alzheimers Dis. 2009;17(3):661-80.
Arendash, G. W., Mori, T., Cao, C., Mamcarz, M., Runfeldt, M., Dickson, A., Rezai-Zadeh, K., Tane, J., Citron, B. A., Lin, X., Echeverria, V., & Potter, H. (2009). Caffeine reverses cognitive impairment and decreases brain amyloid-beta levels in aged Alzheimer's disease mice. Journal of Alzheimer's Disease : JAD, 17(3), 661-80. https://doi.org/10.3233/JAD-2009-1087
Arendash GW, et al. Caffeine Reverses Cognitive Impairment and Decreases Brain Amyloid-beta Levels in Aged Alzheimer's Disease Mice. J Alzheimers Dis. 2009;17(3):661-80. PubMed PMID: 19581722.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Caffeine reverses cognitive impairment and decreases brain amyloid-beta levels in aged Alzheimer's disease mice. AU - Arendash,Gary W, AU - Mori,Takashi, AU - Cao,Chuanhai, AU - Mamcarz,Malgorzata, AU - Runfeldt,Melissa, AU - Dickson,Alexander, AU - Rezai-Zadeh,Kavon, AU - Tane,Jun, AU - Citron,Bruce A, AU - Lin,Xiaoyang, AU - Echeverria,Valentina, AU - Potter,Huntington, PY - 2009/7/8/entrez PY - 2009/7/8/pubmed PY - 2009/12/16/medline SP - 661 EP - 80 JF - Journal of Alzheimer's disease : JAD JO - J. Alzheimers Dis. VL - 17 IS - 3 N2 - We have recently shown that Alzheimer's disease (AD) transgenic mice given a moderate level of caffeine intake (the human equivalent of 5 cups of coffee per day) are protected from development of otherwise certain cognitive impairment and have decreased hippocampal amyloid-beta (Abeta) levels due to suppression of both beta-secretase (BACE1) and presenilin 1 (PS1)/gamma-secretase expression. To determine if caffeine intake can have beneficial effects in "aged" APPsw mice already demonstrating cognitive impairment, we administered caffeine in the drinking water of 18-19 month old APPsw mice that were impaired in working memory. At 4-5 weeks into caffeine treatment, those impaired transgenic mice given caffeine (Tg/Caff) exhibited vastly superior working memory compared to the continuing impairment of control transgenic mice. In addition, Tg/Caff mice had substantially reduced Abeta deposition in hippocampus (decrease 40%) and entorhinal cortex (decrease 46%), as well as correlated decreases in brain soluble Abeta levels. Mechanistically, evidence is provided that caffeine suppression of BACE1 involves the cRaf-1/NFkappaB pathway. We also determined that caffeine concentrations within human physiological range effectively reduce active and total glycogen synthase kinase 3 levels in SweAPP N2a cells. Even with pre-existing and substantial Abeta burden, aged APPsw mice exhibited memory restoration and reversal of AD pathology, suggesting a treatment potential of caffeine in cases of established AD. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/19581722/Caffeine_reverses_cognitive_impairment_and_decreases_brain_amyloid_beta_levels_in_aged_Alzheimer's_disease_mice_ L2 - https://content.iospress.com/openurl?genre=article&issn=1387-2877&volume=17&issue=3&spage=661 DB - PRIME DP - Unbound Medicine ER -