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The Journal of Neuroscience, November 1, 2001, 21(21):8370-8377
The Curry Spice Curcumin Reduces Oxidative Damage and Amyloid
Pathology in an Alzheimer Transgenic Mouse
Giselle P.
Lim1, 3,
Teresa
Chu1, 3,
Fusheng
Yang1, 3,
Walter
Beech1, 3,
Sally A.
Frautschy1, 2, 3, and
Greg M.
Cole1, 2, 3
Departments of 1 Medicine and 2 Neurology,
University of California, Los Angeles, Los Angeles, California 90095, and 3 Greater Los Angeles Veterans Affairs Healthcare
System, Geriatric Research, Education and Clinical Center,
Sepulveda, California 91343
Inflammation in Alzheimer's disease (AD) patients is characterized
by increased cytokines and activated microglia. Epidemiological studies
suggest reduced AD risk associates with long-term use of nonsteroidal
anti-inflammatory drugs (NSAIDs). Whereas chronic ibuprofen suppressed
inflammation and plaque-related pathology in an Alzheimer transgenic
APPSw mouse model (Tg2576), excessive use of NSAIDs targeting
cyclooxygenase I can cause gastrointestinal, liver, and renal toxicity.
One alternative NSAID is curcumin, derived from the curry spice
turmeric. Curcumin has an extensive history as a food additive and
herbal medicine in India and is also a potent polyphenolic antioxidant.
To evaluate whether it could affect Alzheimer-like pathology in the
APPSw mice, we tested a low (160 ppm) and a high dose of dietary
curcumin (5000 ppm) on inflammation, oxidative damage, and plaque
pathology. Low and high doses of curcumin significantly lowered
oxidized proteins and interleukin-1 , a proinflammatory cytokine
elevated in the brains of these mice. With low-dose but not high-dose
curcumin treatment, the astrocytic marker GFAP was reduced, and
insoluble -amyloid (A), soluble A, and plaque burden
were significantly decreased by 43-50%. However, levels of amyloid
precursor (APP) in the membrane fraction were not reduced. Microgliosis
was also suppressed in neuronal layers but not adjacent to plaques. In view of its efficacy and apparent low toxicity, this Indian spice component shows promise for the prevention of Alzheimer's disease.
Key words:
Alzheimer's disease; inflammation; oxidative damage; anti-oxidant; microglia; plaque; interleukin-1; Tg2576; APPswedish
Copyright © 2001 Society for Neuroscience 0270-6474/01/21218370-08$05.00/0
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