Magnesium Supplement to Treat Alzheimer’s Disease

The human brain contains roughly eighty-six billion (~10^10) neurons, each of which forms approximately ten thousand (10^4) synaptic connections with other neurons. Therefore, on average, there are one hundred trillion (10^14) synapses in the brain! Maintaining the health of these synapses is essential for proper brain function and higher cognitive functions like learning, memory, and emotion. Dysfunction of synaptic function is thought to underlie many types of neurodegenerative diseases, including Alzheimer’s disease and aging related dementia. Those affected with Alzheimer’s disease and dementia have severe learning and memory impairments, impaired judgment, severe anxiety and other mood disruptions.

A significant amount of research funding has been devoted to revealing the underlying biological changes that occur in Alzheimer’s disease and age-related dementia with the hope that understanding the cause of these diseases will help scientists and doctors develop new treatments and preventative therapies. Recently, researchers have been investigating how magnesium may be a useful treatment for these devastating diseases. Magnesium (Mg2+) is the fourth most abundant mineral in the body and is necessary for proper enzyme function in nearly every cell of the body, including neurons. In 2004, researchers at MIT demonstrated that Mg2+ helps regulate synapse strength by modulating NMDA receptors [1]. NMDA receptors on neurons play a critical role in synaptic function and are required for proper learning, memory, and emotional stability. Later, a second study from the same group found that aged rats that were given a magnesium supplement had improved memory and learning ability [2]. Interestingly, the amount of Mg2+ in the brain increased by only ~15% during the chronic Mg2+ treatment. Nonetheless, this small increase in brain Mg2+ concentration was sufficient to reduce the memory deficits in aged rats.

In a new article published this month in The Journal of Neuroscience, the same research group demonstrates that magnesium supplement is effective at preventing and reversing cognitive deficits in a mouse model of Alzheimer’s disease [3,4]! The authors utilized a genetically modified mouse strain, “AD-mice”, that possesses two genetic mutations that have been found in humans with early onset Alzheimer’s disease: a mutated amyloid precursor protein and mutated presenilin protein. These mice show significant reduction in learning and memory ability around 6-7 months of age. In one set of experiments, the authors administered daily Mg2+ supplement when the animals reached 6 months of age and then tested their spatial learning and memory one month later or 9 months later. In both experiments, the AD-mice that received magnesium treatment performed as well as normal mice that did not have the mutations. In contrast, AD-mice that did not receive Mg2+ treatment showed severe memory impairments. When the researchers compared the level of Mg2+ in the brains of the mice to their learning ability, they found a strong positive relationship. In other words, mice that performed better had higher brain Mg2+ levels.  To investigate exactly how the Mg2+ treatment prevented the cognitive impairments of AD-mice, they looked at the strength and overall number of synapses in the brain.  Surprisingly, they found that Mg2+ treatment prevented the loss of synapses in the brains of AD-mice and prevented the reduction in synaptic strength!  Moreover, the researchers found that Mg2+ treatment caused a reduction in amyloid-beta deposits in the brain, a classic marker of Alzheimer’s disease. These data showed that Mg2+ supplement prevented the onset of Alzheimer’s disease by preventing the loss of synaptic function.

In a final set of experiments, the authors assessed the cognitive ability of elderly AD-mice (22 months old) that had never received Mg2+ treatment and observed significant cognitive deficits. They then gave Mg2+ supplement to the AD-mice for one month and then tested the same mice again. Amazingly, the Mg2+ treatment was able to reverse the cognitive deficits in the AD-mice and, similar to the results 15 month old mice, strengthened synaptic function.

The results of this study and the previous studies from the Liu research group are quite exciting! Magnesium supplements are relatively cheap, widely available, require no prescription, and are generally well tolerated by the human body. If Mg2+ supplement is shown to have similar effects on cognitive function in humans as in rats and mice, then Mg2+ supplement may become an important preventative measure that could be included in any aging person’s diet as a way to reduce or prevent cognitive decline. Alternatively, those already afflicted with Alzheimer’s disease or dementia may still benefit from Mg2+ treatment similar to the elderly AD-mice used in the study.  We at Knowing Neurons look forward to the results of human trial studies and hope that Mg2+ supplement becomes a viable preventative measure for the aged community.

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Disclosure: Knowing Neurons and its Editors have no financial interest to divulge.

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Written by Ryan Jones.

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References:

1. Slutsky I., Sadeghpour S., Li B. & Liu G. (2004). Enhancement of Synaptic Plasticity through Chronically Reduced Ca2+ Flux during Uncorrelated Activity, Neuron, 44 (5) 835-849. DOI: 10.1016/j.neuron.2004.11.013

2. Slutsky I., Abumaria N., Wu L.J., Huang C., Zhang L., Li B., Zhao X., Govindarajan A., Zhao M.G., Zhuo M. & Tonegawa S. & (2010). Enhancement of Learning and Memory by Elevating Brain Magnesium, Neuron, 65 (2) 165-177. DOI: 10.1016/j.neuron.2009.12.026

3. Abumaria N, Yin B, Zhang L, Li XY, Chen T, Descalzi G, Zhao L, Ahn M, Luo L, Ran C, Zhuo M, Liu G (2011). Effects of Elevation of Brain Magnesium on Fear Conditioning, Fear Extinction, and Synaptic Plasticity in the Infralimbic Prefrontal Cortex and Lateral Amygdala. J Neurosci 31:14871–14881. DOI: 10.1523/JNEUROSCI.3782-11.2011 

4. Li W., Yu J., Liu Y., Huang X., Abumaria N., Zhu Y., Huang X., Xiong W., Ren C., Liu X.G. & Chui D. & (2013). Elevation of Brain Magnesium Prevents and Reverses Cognitive Deficits and Synaptic Loss in Alzheimer’s Disease Mouse Model, Journal of Neuroscience, 33 (19) 8423-8441. DOI:10.1523/JNEUROSCI.4610-12.2013

Images adapted from Corbis and made by Kate Jones.