Inflammation and Alzheimer’s Disease

In America alone, every 70 seconds, someone develops Alzheimer's disease.¹ The brain of a person with Alzheimer’s disease is progressively destroyed by the formation of plaques, caused by deposits of a protein called beta-amyloid, and tangles, caused by a protein called tau. In a healthy person, beta-amyloid is broken down and removed from the brain.

But in the person with Alzheimer’s disease, the beta-amyloid pieces accumulate and harden into plaques, while the tau protein interferes with the transfer of nutrients and other important substances between cells. Free radical activity (free radicals are unstable compounds that can damage cells and our DNA) is also higher in the brains of people with Alzheimer’s disease. 

The early stage of AD is characterized by forgetfulness, communication problems, and changes in mood and behavior. Judgment is impaired, and sometimes people with AD say rude things they would never have said aloud prior to their illness.  This alone can cause problems between couples, families and friends. Finding a way to stop the disease, or at least slow its progression, has been a top priority for researchers around the world.

What continues to be investigated is what factors cause these physical changes in the first place. We know that inflammation and oxidative damage plays a role, as does diet, body weight, activity levels, past head injuries, family history, presence of other diseases, certain contaminants (especially aluminum), and even the amount of social connections.

The plaques and tangles associated with Alzheimer’s disease (AD) form in the brain in a predictable pattern. They first attack areas of the brain associated with memory and learning. As the disease progresses, memory and thinking continue to decline. The ability to carry out daily tasks and self-care becomes more and more limited. In the very last stages of AD, the ability to communicate verbally and care for oneself is completely lost.  Many people with AD succumb to pneumonia, as they can no longer walk about, choke easily as they are fed, and spend much time immobile in bed.

The initial cause of Alzheimer’s disease – of what sets it in motion -- is not entirely known. Inflammation is certainly a factor, because it spurs the accumulation of plaques and tangles to have even more damaging effects. And the traditional diet of India is one reason why curcumin is being seriously considered as a treatment option.

Much Lower Rate of Alzheimer’s Disease in India

The rate of AD in India is about 4.4-fold less than that of the United States. While there are probably many factors that account for the difference, the fact that curcumin is consumed daily in curry spice from a very early age can’t be overlooked. Even though the daily amount of actual curcumin from turmeric is smaller in that case, the cumulative effect is considerable.

So in recent years, researchers have been looking at the effects of curcumin extracts – which have much higher levels of the compound than dietary turmeric – for treating AD.^2,3

Curcumin Stops Brain-Harming Inflammation

The connection between inflammation and Alzheimer’s can’t be overstated. Neurons are especially susceptible to inflammation or other injury, and the release of inflammatory compounds in the body can be neurotoxic. This includes tumor necrosis factor-alpha (TNF-a), interleukin-1-beta (IL-1β), free radicals, including nitric oxide (NO) and others. Curcumin has a great potential for a therapeutic role because it works through multiple inflammatory pathways:

1. Inhibits the activity of TNF, one of the most pro-inflammatory cytokines (cell-signaling protein molecules)
2. Suppresses the activation of the NF-kB, which regulates the expression of pro-inflammatory gene products
3. >Downregulates COX-2 – the enzyme linked to most inflammation
4. Inhibits 5-LOX, another pro-inflammatory enzyme
5. Downregulates the expression of cell surface adhesion molecules linked to inflammation

Although Alzheimer’s has a genetic component, there too, the connection to inflammation is very strong. Some people are simply predisposed to inflammation more than others. Research has found that polymorphisms (small variations in the DNA) in the receptor gene for IL-1 (a pro-inflammatory cytokine) can increase the risk of AD as much as 3 times.

Curcumin Protects Brains Cells, Sweeps Away Plaques

So far, much of the research surrounding curcumin and Alzheimer’s has been done in laboratory studies using experimental models of AD in mice. However, the results have been very positive so far. In fact, one study found that curcumin protected brain cells damaging inflammation, reduced beta-amyloid levels, and shrank the size of accumulated plaques by over 30%.²

Curcumin is able to do this because it binds to aggregated amyloid beta plaques, and prevents them from enlarging further. It also blocks the formation of new plaques.

Because non-steroidal anti-inflammatory drugs (NSAIDs) have shown some preventive effect on amyloid beta plaques, one study compared ibuprofen and curcumin for their ability to protect against amyloid beta protein damage.

Both treatments reduced the activation of microglial cells, showing that they reduced inflammation in the brain. (Microglial cells react to inflammation and shuttle waste material out of the central nervous system, and have a protective effect.)

But, only curcumin reduced microgliosis within and adjacent to the plaque deposits, so it provided a much more targeted approach. And between the two, only curcumin stopped oxidative damage. This study also showed that curcumin prevented spatial memory loss and reduced amyloid beta deposits.⁴

Further studies have expanded on these findings. In another laboratory study, researchers noted that curcumin binds to the beta-amyloid, stopped aggregation, and actually broke up amyoid-beta plaques.⁵

Curcumin Flushes Away Harmful Metals from the Brain

The effects of metals (including copper, iron, and others) as possible causes of Alzheimer’s has long been discussed because these minerals can cause amyloid beta aggregation and are often found concentrated in the brain tissue of those affected by Alzheimer’s disease.

Here again, curcumin is very useful. It binds to copper and iron, essentially helping to “flush” the metals from brain tissue, and stop any potential harm -- especially their ability to induce NF-kappa-B inflammatory action. Curcumin has also been shown to protect against lead and cadmium induced damage as well.⁶

Exciting Curcumin – Hope for the Future

Still other studies have shown that curcumin helps regenerate neurons, providing a possibility of “rewiring” neural patterns and at the very least, delaying the ultimate effects of the disease. These properties – and lack of side effects – means that curcumin has great potential utility in addressing Alzheimer’s.³

While the studies surrounding curcumin and Alzheimer’s are ongoing, there is clinical research that is especially notable, taking place at the McCusker Alzheimer’s Research Foundation. This institute, supporting research at Edith Cowan University in Perth, Australia, is currently administering a highly absorbable form of curcumin to patients with mild to moderate dementia. Their goal is to learn as much as possible how curcumin can be used as an effective treatment for AD.⁷

The research surrounding curcumin and Alzheimer’s is exciting, but there is certainly more work to be done. As of yet, curcumin isn’t a “cure” for Alzheimer’s, but it may help those suffering from the disease to hold on to memories and cognitive function longer.

References:

1. ^{Alzheimer’s Association. “Alzheimer’s Facts and Figures.” Available at: http://www.alz.org/alzheimers_disease_facts_and_figures.asp?gclid=CISdv-SfvLcCFc0WMgodyWwAGQ#prevalence. Accessed: May 29, 2013.}
2. ^{Zhang C, Browne A, Child D, Tanzi RE. Curcumin decreases amyloid-beta peptide levels by attenuating the maturation of amyloid-beta precursor protein. J Biol Chem. 2010;285(37):28472-80.}
3. ^{Garcia-Alloza M. Curcumin labels amyloid pathology in vivo, disrupts existing plaques, and partially restores distorted neurites in an Alzheimer mouse model. J Neurochem. 2007;102:1095-1104.}
4. ^{Frautschy SA, Hu W, Kim P, Miller SA, Chu T, Harris-White ME, Cole GM. Phenolic anti-inflammatory antioxidant reversal of Abeta-induced cognitive deficits and neuropathology. Neurobiol Aging. 2001 Nov-Dec;22(6):993-1005.}
5. ^{Yang F, Lim GP, Begum AN, Ubeda OJ, Simmons MR, Ambegaokar SS, Chen PP, Kayed R, Glabe CG, Frautschy SA, Cole GM. Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo. J Biol Chem. 2005 Feb 18;280(7):5892-901.}
6. ^{Baum L, Ng A. Curcumin interaction with copper and iron suggests one possible mechanism of action in Alzheimer's disease animal models. J Alzheimers Dis. 2004 Aug;6(4):367-77; discussion 443-9.}
7. ^{Martins R. Evaluation of the nutritional extract Bio-curcumin (BCM-95) to preserve cognitive functioning in a cohort of mild cognitively impaired (MCI) patients over 12 months. Edith Cowan University. Joondalup, Western Australia.}