Date: 27 Oct 2006 18:25:53
From: Mark Thorson
Subject: Coffee Protective Against Alzheimer's Disease
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Neuroscience. 2006 Aug 25
Caffeine protects Alzheimer's mice against cognitive
impairment and reduces brain beta-amyloid production.
Arendash GW, Schleif W, Rezai-Zadeh K, Jackson EK,
Zacharia LC, Cracchiolo JR, Shippy D, Tan J.
The Byrd Alzheimer's Center and Research Institute,
Tampa, FL 33647, USA; Memory and Aging Research
Laboratory, SCA 110, 4202 East Fowler Avenue,
University of South Florida, Tampa, FL 33620, USA.
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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Note that these are not ordinary mice. They
are "transgenic" mice, which have been given
the gene for human beta-amyloid precursor protein.
These "humanized" mice are a far closer model
to human Alzheimer's disease than any other
animal model. They permit experiments that
would be unethical, take too long, and cost
too much money if performed on humans. For
more information about these transgenic mice,
see: http://www.taconic.com/anmodels/001349.htm
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