The Curcumin Advantage
Even if NSAIDs are proven as effective as curcumin as a prophylaxis for Alzheimer’s disease, researchers are not heralding these anti-inflammatory drugs in the long-term struggle against Alzheimer’s. The reason for their reticence is simple: NSAIDs have potentially lethal side effects. According to the UCLA research team, “A principal limitation precluding widespread NSAID use for prevention of Alzheimer’s disease is gastrointestinal and occasional liver and kidney toxicity caused by inhibiting cyclooxygenase-1 [an enzyme that protects the stomach lining]. Side-effect issues could be overcome using alternative anti-inflammatory drugs directed against different inflammatory targets.”21

One such anti-inflammatory agent, they postulated, is curcumin, which may offer powerful protection for humans as well as mice. Curcumin’s antioxidant effects are central to its promise, as scientists have determined that the pathology of Alzheimer’s involves oxidative damage that correlates directly with the beta amyloid deposits that typically characterize the disease.22 In this vicious cycle, oxidative stress promotes the production of beta amyloid in the brain, and increasing levels of beta amyloid inflict greater levels of oxidative damage.

Mystery Waiting to Be Solved
Although curcumin shows great promise as an agent for preventing Alzheimer’s disease, many questions remain to be answered. Scientists still are not completely certain of curcumin’s mechanism of action against neuronal plaques, though they do know that it inhibits many of the body’s inflammatory mediators. In fact, studies have found that curcumin retards the action of molecules such as phospholipase, lipooxygenase, cyclooxygenase-2 (COX-2), leukotrienes, thromboxane, prostaglandins, nitric oxide, collagenase, elastase, hyalur-onidase, monocyte chemoattractant protein-1 (MCP-1), interferon-inducible protein, tumor necrosis factor, and interleukin-12.23

Recent research suggests that oxidation caused by free radicals in the brain sparks neuronal toxicity, not only in Alzheimer’s disease but possibly in other neurodegenerative disorders such as Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis.24 These disorders likewise have been associated at the molecular level with free-radical-induced mutation, oxidative enzyme impairment, and mitochondrial dysfunction.24

Some experts believe an antioxidant molecule known as glutathione plays a central role in the evolutionary events in the brain that lead to oxidation. “[Glutathione] plays multiple roles in the nervous system, including free radical scavenger, redox modulator of ionotropic receptor activity, and possible neurotransmitter,” wrote investigators from the University of British Columbia in 1997.25

Other experts have noted that brain cell abnormalities, specifically in the cells’ mitochondria, may contribute to the abnormal production of free radicals in the brain.25 Abnormal mitochondrial function leads to dysfunction of cytochrome-c oxidase, a necessary mitochondrial enzyme that in turn may contribute to the abnormal production of free radicals, thus causing levels of beta amyloid to increase. As the vicious cycle continues, beta amyloid attracts even more free radicals.

“The free radical hypothesis can account for the vastly heterogeneous nature of Alzheimer’s disease and the fact that both genetic and nongenetic causes are involved,” wrote one expert. “Such general considerations suggest that free radicals are involved in many age-related pathologies, specifically in Alzheimer’s disease and all neurodegenerative diseases.”26

The inflammation and destructive oxidation inherent in Alzheimer’s are why antioxidants like curcumin may be so effective in preventing progression of the disease. By its very nature, curcumin fends off free radicals, preventing their destructive effects in the illness’s very earliest stages. Antioxidants not only target free radicals in the brain, but also possess powerful anti-inflammatory mechanisms, another reason why curcumin may be efficacious against Alzheimer’s disease.27 These dual mechanisms of protection against inflammation and oxidative damage make curcumin a particularly promising natural agent in fighting the ravages of aging and degenerative diseases.