Curcumin More Effective than Drugs for Alzheimer's

Curcumin, from tumeric, is the yellow pigment in curry spice. It was found it to be more effective in mice than drugs currently being investigated for Alzheimer's disease treatment.
A dietary staple of India, where Alzheimer's disease rates are among the world's lowest, curcumin appears to block and break up brain plaques that cause the disease.

Curcumin has also been found to correct the cystic fibrosis defect in mice, prevent the onset of alcoholic liver disease and may slow down the blood cancer multiple myeloma as well as multiple sclerosis.

Reporting in the December 2004 online edition of the Journal of Biological Chemistry, researchers from the University of California Los Angeles also revealed that curcumin is more effective in inhibiting formation of the protein fragments than many other drugs being tested as Alzheimer's treatments.

The researchers found the low molecular weight and polar structure of curcumin allow it to penetrate the blood-brain barrier effectively and bind to beta amyloid (which form the disease-causing plaques). In earlier studies published during 2001, the same UCLA research team found curcumin has powerful antioxidant and anti-inflammatory properties, which scientists believe help ease Alzheimer's symptoms caused by oxidation and inflammation.

The body of research has prompted the UCLA Alzheimer's Disease Research Center (ADRC) to begin human clinical trials to further evaluate its protective and therapeutic effects.
"The prospect of finding a safe and effective new approach to both prevention and treatment of Alzheimer's disease is tremendously exciting," said principal investigator Gregory Cole, professor of medicine and neurology at the David Geffen School of Medicine at UCLA and associate director of the UCLA Alzheimer's Disease Research Center.
"Curcumin has been used for thousands of years as a safe anti-inflammatory in a variety of ailments as part of Indian traditional medicine," Cole added.

"Recent successful studies in animal models support a growing interest in its possible use for diseases of ageing involving oxidative damage and inflammation like Alzheimer's, cancer and heart disease. What we really need, however, are clinical trials to establish safe and effective doses in aging patients."

Alzheimer's disease is the most common form of dementing illness among middle and older adults, affecting more than 4 million Americans and many millions worldwide. The prevalence of Alzheimer's among adults aged 70-79 in India, however, is 4.4 times less than the rate in the United States.

Abstract

Alzheimer's disease (AD) involves amyloid (A) accumulation, oxidative damage, and inflammation, and risk is reduced with increased antioxidant and anti-inflammatory consumption. The phenolic yellow curry pigment curcumin has potent anti-inflammatory and antioxidant activities and can suppress oxidative damage, inflammation, cognitive deficits, and amyloid accumulation.

Since the molecular structure of curcumin suggested potential A binding, we investigated whether its efficacy in AD models could be explained by effects on A aggregation. Under aggregating conditions in vitro, curcumin inhibited aggregation (IC50 = 0.8 µM) as well as disaggregated fibrillar A40 (IC50 = 1 µM), indicating favorable stoichiometry for inhibition.

Curcumin was a better A40 aggregation inhibitor than ibuprofen and naproxen, and prevented A42 oligomer formation and toxicity between 0.1 and 1.0 µM. Under EM, curcumin decreased dose dependently A fibril formation beginning with 0.125 µM. The effects of curcumin did not depend on A sequence but on fibril-related conformation. AD and Tg2576 mice brain sections incubated with curcumin revealed preferential labeling of amyloid plaques. In vivo studies showed that curcumin injected peripherally into aged Tg mice crossed the blood-brain barrier and bound plaques. When fed to aged Tg2576 mice with advanced amyloid accumulation, curcumin labeled plaques and reduced amyloid levels and plaque burden. Hence, curcumin directly binds small -amyloid species to block aggregation and fibril formation in vitro and in vivo.

These data suggest that low dose curcumin effectively disaggregates A as well as prevents fibril and oligomer formation, supporting the rationale for curcumin use in clinical trials preventing or treating AD.

Reference:

Fusheng Yang, Giselle P. Lim, Aynun N. Begum, Oliver J. Ubeda, Mychica R. Simmons, Surendra S. Ambegaokar, Pingping P. Chen, Rakez Kayed, Charles G. Glabe, Sally A. Frautschy, and Gregory M. Cole. Curcumin Inhibits Formation of Amyloid Oligomers and Fibrils, Binds Plaques, and Reduces Amyloid in Vivo. J. Biol. Chem., Vol. 280, Issue 7, 5892-5901, February 18, 2005

Key concepts: curcumin, turmeric, brain, alzheimer's disease, dementia