Degree Granting Department
Gary Arendash, Ph.D.
Amyloid, S-adenosylmethionine, PS1, Adenosine, Transgenic mice
A recent epidemiological study suggested that higher caffeine intake reduces the risk of Alzheimer's disease (AD). Caffeine, a widely consumed stimulatory drug, is a non-selective adenosine receptor antagonist that has been shown to increase plasma adenosine levels in rodents. To determine any long-term protective effects of caffeine in a controlled longitudinal study, caffeine was added to the drinking water of APPsw transgenic (Tg) mice between 4 and 9 1/2 months of age, with behavioral testing done during the last 6 weeks of treatment. The average daily intake of caffeine per mouse (1.5 mg) was the human equivalent of 5 cups of coffee/day. Across multiple cognitive tasks of spatial learning/reference memory, working memory, and recognition/identification, Tg mice given caffeine (Tg+Caff) performed significantly better than Tg control mice and similar to non-transgenic controls. Discriminant Function Analysis involving multiple cognitive measures clearly showed the
superior overall cognitive performance of Tg+Caff mice compared to Tg controls. Analysis of amyloid beta in the hippocampus by ELISA revealed Tg+Caff mice had significantly less soluble amyloid beta 1-40 and insoluble amyloid beta 1-42. In a follow-up study involving neurochemical analysis only, caffeine was added to the drinking water of 17 month old APPsw mice for 18 days. In this study, Tg+Caff mice also showed a significant reduction of insoluble amyloid beta 1-42 in the hippocampus. In contrast to the reduced extracellular brain levels of adenosine in Tg controls, caffeine treatment normalized brain adenosine levels in Tg mice to that of non-transgenic controls. Analysis of amyloidogenic secretase activity revealed the reduction in amyloid beta is likely because of a reduction in gamma secretase activity as a result of increased SAM silencing of PS1 expression. This study suggest that a modest, long-term caffeine intake of approximately 500 mg per day (5 cups of coffee) may redu
ce considerably the risk of AD by decreasing amyloidogenesis.
Scholar Commons Citation
Schleif, William, "Effects of long-term administration of caffeine in a mouse model for Alzheimer's disease" (2005). Graduate Theses and Dissertations.