The Curry Spice Curcumin Reduces Oxidative Damage and Amyloid Pathology in an Alzheimer Transgenic Mouse

Abstract

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-1beta, 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 beta-amyloid (Abeta), soluble Abeta, 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.

Targeting the Prodromal Stage of Alzheimer's Disease: Bioenergetic and Mitochondrial Opportunities

“…In addition to its strong antioxidant ability, it has anti-inflammatory activity, reduces amyloid plaque burden, and partially restored distorted neuritis [125][126][127][128]. A current Phase II clinical trial that combines curcumin and yoga therapy aims to treat MCI (ClinicalTrials.gov identifier: NCT01811381).…”

Free radical-mediated damage to brain in Alzheimer's disease and its transgenic mouse models

“…Orally administered curcumin reduces brain protein carbonyls and Aβ burden in Tg2576 mice [80], even when initiated after the age of plaque formation [81]. Another readily available and non-toxic antioxidant is melatonin.…”

Prevention of Alzheimer's disease: Omega-3 fatty acid and phenolic anti-oxidant interventions

“…Although other groups have some evidence for protection, in our hands, neither ibuprofen nor Vitamin E supplements reduced protein carbonyls, one marker for oxidative damage. In contrast, a polyphenolic tumeric component, diferulomethane (curcumin) lowered F2 isoprostanes and carbonyls as measures of oxidative damage, reduced IL-1␤, iNOS and CD11b as markers of activated microglia and limited cognitive deficits, postsynaptic marker loss and amyloid accumulation [9,15].…”

“…Since this compound has multiple direct and indirect anti-amyloid actions including metal chelating, phagocytosis enhancing, anti-oxidant and cholesterol-lowering activity (reviewed in refs. [15,33] and possible suppression of BACE1 induction, it is likely that no one mechanism is involved. Curcumin also inhibits known amyloid response pathways including JNK kinase and iNOS expression in vitro [5,12,23] and in vivo [10,13] and in CNS (our data).…”