AbstractA recent epidemiological study

suggested that
higher caffeine intake over decades reduces the risk
of Alzheimers
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 nal 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 ve
cups of
coffee per day. Across multiple cognitive tasks of
spatial
learning/reference memory, working memory, and
recognition/identication,
Tg mice given caffeine performed signicantly
better than Tg control mice and similar to
nontransgenic
controls. In both behaviorally-tested and aged
Tg mice, long-term caffeine administration resulted
in
lower hippocampal
-amyloid (A) levels. Expression of
both Presenilin 1 (PS1) and
-secretase (BACE) was reduced
in caffeine-treated Tg mice, indicating decreased A
production as a likely mechanism of caffeines
cognitive
protection. The ability of caffeine to reduce A
production
was conrmed in SweAPP N2a neuronal cultures,
wherein
concentration-dependent decreases in both A
140 and

Abstrak-Sebuah studi epidemiologi terbaru

menunjukkan bahwa
asupan kafein yang lebih tinggi selama beberapa
dekade mengurangi risiko Alzheimer
Penyakit (AD). Penelitian ini berusaha untuk
menentukan
efek protektif jangka panjang asupan kafein diet
dalam studi longitudinal terkontrol melibatkan
transgenik AD
tikus. Kafein (reseptor antagonis adenosin) adalah
ditambahkan ke air minum amiloid protein
prekursor,
Swedia mutasi (APPsw) transgenik (Tg) tikus
antara 4
dan 9 bulan usia, dengan pengujian perilaku
dilakukan selama
fi nal 6 minggu pengobatan. Rata-rata asupan
harian
kafein per tikus (1,5 mg) adalah sama manusia
500 kafein mg, jumlah biasanya ditemukan di lima
cangkir
kopi per hari. Di beberapa tugas kognitif spasial
pembelajaran / memori referensi, memori kerja, dan
pengakuan / identifikasi,
tikus Tg diberikan kafein dilakukan secara
signifikan
lebih baik daripada tikus kontrol Tg dan mirip
dengan nontransgenik
kontrol. Dalam kedua perilaku-diuji dan berusia
Tg tikus, administrasi kafein jangka panjang
mengakibatkan
hippocampal rendah
? -amyloid (A?) Tingkat. ekspresi
kedua Presenilin 1 (PS1) dan
? -secretase (BACE) dikurangi
kafein yang diobati Tg tikus, menunjukkan
penurunan A
?
produksi sebagai mekanisme kemungkinan kognitif
kafein
perlindungan. Kemampuan kafein untuk
mengurangi A
? produksi
itu con fi rmed di SweAPP N2a budaya neuronal,
dimana
tergantung konsentrasi menurun di kedua A
? 1-40 dan
SEBUAH

A
142 were observed. Although adenosine A
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
1
G.W.A. and W.S. contributed equally to this work.
*Correspondence to: G. W. Arendash, Memory and
Aging Research
Laboratory, SCA 110, 4202 East Fowler Avenue,
University of South
Florida, Tampa, FL 33620, USA. Tel: 1-813-9741584; fax:
1-813-974-3263.
E-mail address: arendash@cas.usf.edu (G. W.
Arendash).
Abbreviations: A
, -amyloid; AD, Alzheimers disease; ANOVA,
analysis
of variance; APPsw, amyloid precursor protein,
Swedish mutation;
BACE,
-secretase; DFA, discriminant factor analysis; ESI,
electrospray
ionization source; FA, factor analysis; FOR, formic
acid; LSD,
least signicant difference; MR, metabolic rate; NT,
non-transgenic;
OD, optical density; PD, Parkinsons disease; PS1,
Presenilin 1;
RAWM, radial arm water maze; TBS, Tris-buffered
saline; Tg, transgenic;
TgCaff, transgenic mice given caffeine.
c
1
d
or A
0306-4522/06$30.000.00 2006 IBRO. Published
by Elsevier Ltd. All rights reserved.
doi:10.1016/j.neuroscience.2006.07.021
2A
941

? 1-42 diamati. Meskipun adenosin A

kepadatan reseptor di korteks atau hippocampus
tidak terpengaruh
dengan perlakuan kafein, adenosine otak tingkat di
Tg
tikus dikembalikan kembali normal dengan kafein
diet dan
bisa terlibat dalam perlindungan kognitif yang
disediakan oleh
kafein. Data kami menunjukkan bahwa asupan
harian moderat
1
G.W.A. dan W.S. kontribusi sama untuk pekerjaan
ini.
* Korespondensi ke: G. W. Arendash, Memory dan
Aging Penelitian
Laboratorium, SCA 110, 4202 East Fowler Avenue,
University of South
Florida, Tampa, FL 33620, USA. Telp: 1-813-9741584;? fax:
? 1-813-974-3263.
Alamat E-mail: arendash@cas.usf.edu (G. W.
Arendash).
Singkatan: A
??, -amyloid; AD, penyakit Alzheimer; ANOVA,
analisis
varians; APPsw, prekursor amiloid protein, mutasi
Swedia;
BACE,
? -secretase; DFA, analisis faktor diskriminan; ESI,
electrospray
sumber ionisasi; FA, analisis faktor; UNTUK, asam
format; LSD,
Setidaknya signi fi perbedaan tidak bisa; MR,
tingkat metabolisme; NT, non-transgenik;
OD, densitas optik; PD, penyakit Parkinson; PS1,
Presenilin 1;
RAWM, radial labirin air lengan; TBS, Trisbuffered saline; Tg, transgenik;
Tg? Caff, tikus transgenik diberikan kafein.
c
1
d
atau A
0306-4522 / 06 $ 30,00? 0.00 2006 IBRO.
Diterbitkan oleh Elsevier Ltd All rights reserved.
doi: 10,1016 / j.neuroscience.2006.07.021
2A

of caffeine may delay or reduce the risk of AD.

2006
IBRO. Published by Elsevier Ltd. All rights
reserved.
Key words: learning, memory, transgenic mice,
PS1, BACE,
adenosine.

941
kafein dapat menunda atau mengurangi risiko AD.
2006
IBRO. Diterbitkan oleh Elsevier Ltd All rights
reserved.
Kata kunci: pembelajaran, memori, tikus
transgenik, PS1, BACE,
adenosin.