Linked Life Data

19581722

Source:http://linkedlifedata.com/resource/pubmed/id/19581722

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pubmed-article:19581722pubmed:abstractTextWe 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.lld:pubmed
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pubmed-article:19581722pubmed:articleTitleCaffeine reverses cognitive impairment and decreases brain amyloid-beta levels in aged Alzheimer's disease mice.lld:pubmed
pubmed-article:19581722pubmed:affiliationDepartment of Cell Biology, Florida Alzheimer's Disease Research Center, University of South Florida, Tampa, FL 33620, USA. arendash@cas.usf.edulld:pubmed
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pubmed-article:19581722pubmed:publicationTypeResearch Support, N.I.H., Extramurallld:pubmed
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