Red wine might be good for your brain. You’re welcome. Researchers have been investigating the link between aging and cognitive decline, and have identified resveratrol (present in red wine, blueberries, and peanuts, among other foods) as an important potential contributor to treatment strategies. So far, we’ve examined resveratrol’s impacts on cardiovascular disease and diabetes. Today, we’re going to put the spotlight on a different type of chronic disease: Alzheimer’s disease.
Background
Alzheimer’s disease (AD) is an abnormal form of age-related cognitive decline and the most common form of dementia. Although it typically occurs in people over 65 years of age, it can present itself in individuals as young as 40 years old. AD begins with symptoms of mild memory loss and progresses to deepening confusion, mood changes, and physical difficulties such as problems with walking. In the final stages of the disease, the affected person is no longer able to interact appropriately with others or with his or her environment. There is currently no cure; once symptoms start to become apparent, life expectancy is approximately eight years. Current treatment approaches include medications and non-drug therapies to help with memory loss, sleep problems, and mood disorders such as anxiety and depression. AD is the sixth leading cause of death in the United States, and a great deal of effort is going into discovering treatment and prevention strategies.
Physiology of Alzheimer’s disease
We can attribute our abilities to think, speak, and form memories to the approximately 100 billion nerve cells (neurons) that make up our brains. These neurons communicate through electrical signals that pass from cell to cell at junctions called synapses. AD kills neurons, shrinking the brain. The cerebral cortex and hippocampus, which are vital to thinking and memory, are severely damaged. Abnormal protein fragments known as beta-amyloids accumulate in plaques between nerve cells, hindering the transmission of signals. They can also trigger an immune response and inflammation within the brain. Another protein called tau, which is essential to intracellular transport, twists into strands called tangles. Tangles prevent cells from moving nutrients properly and eventually kill them. Plaques and tangles are thought to be the primary hallmarks of AD, therefore, preventing them is a key focus in current research.
Resveratrol’s role
Resveratrol has therapeutic potential for AD in several different ways. It can inhibit the formation and aid in the clearance of beta-amyloid proteins, thus limiting plaque buildup in the brain. It may also trigger degradation of tau proteins and reduce tangles. It has beneficial implications for cell structures called mitochondria, which are involved with energy production and metabolism and are often negatively impacted by aging and AD. When mitochondria malfunction, they can produce reactive oxygen species (ROS) that harm cell tissue. Resveratrol counteracts this by preserving mitochondrial function and scavenging the ROS as an antioxidant. It can also serve as a potent anti-inflammatory agent by blocking certain pathways. Medications that reduce inflammation in the brain have been effective in slowing down AD progression, so this has exciting implications for resveratrol as a potential pharmacological agent.
Finally, resveratrol may hinder telomere shortening. You may have heard of telomeres as the magic key to immorality, and in a way, you wouldn’t be too far off. Telomeres are structures at the end of chromosomes, which carry DNA within cells. They protect chromosomes from degradation; you can think of them sort of like the cap at the end of a shoelace. When they shorten, this makes DNA more vulnerable to harm and cells more vulnerable to death. Telomere shortening is associated with aging and AD. Resveratrol may obstruct this by helping enzymes that maintain and add to telomere length and preventing ROS from damaging telomeres.
Implications for human treatment
I’ve dug into the science and thrown the word “potential” around a lot here, but what does this really mean for us? Again, most of the data on the mechanisms that I’ve described above have come from animal studies. That’s because it’s easier to use model organisms such as mice to figure out what pathways we should be targeting; by the time we get to human clinical trials, we’re really trying to figure out if the treatment works and if it’s safe.
Population data have associated resveratrol with a lower risk of developing AD. Clinical human data have shown that resveratrol is able to reach the brain and affect some of the key proteins and pathways discussed above. However, we’re still not sure exactly how much these effects mean in the larger picture of disease progression. More research will be needed before we can connect the large-scale epidemiological findings to the effects found in current small-scale human studies. Research is ongoing; several active clinical trials are currently recruiting and others are in the process of examining resveratrol’s efficacy as a supplement in treating cognitive impairment and AD. It’s a potentially attractive compound for drug companies; a quick review of conflict of interest statements in published articles reveals that pharmaceutical giants such as Pfizer Inc. and Merck & Co., Inc. have given research grants to scientists studying resveratrol and AD. Hopefully, these efforts will soon translate into treatment strategies to ameliorate suffering for the approximately 46.8 million people living with dementia worldwide.
References
Cai, Zhiyou, Liang-Jun Yan, and Anna Ratka. “Telomere shortening and Alzheimer’s disease.” Neuromolecular Medicine 15.1 (2013): 25-48.
ClinicalTrials.gov [Internet]. (2016). Bethesda (MD): National Library of Medicine (US). Accessed 1 September 2016.
Gocmez, Semil Selcen, et al. “Protective effects of resveratrol on aging-induced cognitive impairment in rats.” Neurobiology of Learning and Memory 131 (2016): 131-136.
Granzotto, Alberto, and Paolo Zatta. “Resveratrol and Alzheimer’s disease: message in a bottle on red wine and cognition.” Frontiers in Aging Neuroscience 6 (2014): 95.
Marambaud, Philippe, Haitian Zhao, and Peter Davies. “Resveratrol promotes clearance of Alzheimer’s disease amyloid-β peptides.” Journal of Biological Chemistry 280.45 (2005): 37377-37382.
Turner, R. Scott, et al. “A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease.” Neurology 85.16 (2015): 1383-1391.
“What is Alzheimer’s?” Alzheimer’s Association. Accessed 1 September 2016.
World Alzheimer’s Association. (2015). World Alzheimer Report 2015 – The Global Impact of Dementia: An analysis of prevalence, incidence, cost and trends. London, UK: Prince, Martin et al.