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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2009-11-23
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pubmed:abstractText |
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.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:issn |
1875-8908
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pubmed:author |
pubmed-author:ArendashGary WGW,
pubmed-author:CaoChuanhaiC,
pubmed-author:CitronBruce ABA,
pubmed-author:DicksonAlexanderA,
pubmed-author:EcheverriaValentinaV,
pubmed-author:LinXiaoyangX,
pubmed-author:MamcarzMalgorzataM,
pubmed-author:MoriTakashiT,
pubmed-author:PotterHuntingtonH,
pubmed-author:Rezai-ZadehKavonK,
pubmed-author:RunfeldtMelissaM,
pubmed-author:TagaM SMS
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pubmed:issnType |
Electronic
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pubmed:volume |
17
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
661-80
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:19581722-Age Factors,
pubmed-meshheading:19581722-Alzheimer Disease,
pubmed-meshheading:19581722-Amyloid beta-Peptides,
pubmed-meshheading:19581722-Amyloid beta-Protein Precursor,
pubmed-meshheading:19581722-Animals,
pubmed-meshheading:19581722-Brain,
pubmed-meshheading:19581722-Caffeine,
pubmed-meshheading:19581722-Cell Line, Transformed,
pubmed-meshheading:19581722-Central Nervous System Stimulants,
pubmed-meshheading:19581722-Cognition Disorders,
pubmed-meshheading:19581722-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:19581722-Disease Models, Animal,
pubmed-meshheading:19581722-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:19581722-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:19581722-Glycogen Synthase Kinase 3,
pubmed-meshheading:19581722-Humans,
pubmed-meshheading:19581722-Maze Learning,
pubmed-meshheading:19581722-Mice,
pubmed-meshheading:19581722-Mice, Transgenic,
pubmed-meshheading:19581722-Models, Biological,
pubmed-meshheading:19581722-Neurons,
pubmed-meshheading:19581722-Presenilin-1,
pubmed-meshheading:19581722-Proto-Oncogene Proteins c-raf,
pubmed-meshheading:19581722-Psychomotor Performance
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pubmed:year |
2009
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pubmed:articleTitle |
Caffeine reverses cognitive impairment and decreases brain amyloid-beta levels in aged Alzheimer's disease mice.
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pubmed:affiliation |
Department of Cell Biology, Florida Alzheimer's Disease Research Center, University of South Florida, Tampa, FL 33620, USA. arendash@cas.usf.edu
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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