Within the journal Science, University of Pittsburgh Graduate School of Public Health scientists confirm that a study which was performed on a mouse model with Alzheimer’s disease, when treated with an anti-cancer drug, significantly improved its brain function and memory capabilities. The cancer drug, known as bexarotene, which was previously studied and used for cullaneous T-cell Lymphoma, was shown to drastically improve the level of cognitive deficits within the brains of mice that were expressing gene mutations that were linked to human Alzheimer’s disease, but the study could not confirm the effect it had on amyloids plaque, the build-up of toxic proteins in the brain that effectively leads to a number of brain-damaging diseases, including Alzheimer’s.
Dr. Rada Koldamova, M.D and Ph.D., senior author and associate professor at Pitt Public said with confidence that the continual study of bexarotene for therapeutic treatment of Alzheimer’s disease. For this study, Dr. Koldamova and her team studied mice that expressed human Apoliopoprotein E4 (APOE4), otherwise known as the only genetic risk factor for Alzheimer’s disease. Bexarotene is chemically related to vitamin A and activates Retinoic X Receptors (RXR) all over the body, and once activated, they bind to DNA, and regulate gene expression of many biological processes, with a consequence of increased levels of APOE4, thanks to RXR activation by bexarotene.
Results of the study showed that male and female mice responded equally, and that after ten days of beginning the testing with bexarotene, mice that genetically expressed human Alzheimer’s APOE3 or APOE4 were able to perform as well in cognitive testing as their non-Alzheimer’s counterpart mice. The drug testing did not affect the mice’s overall weight or behavior, merely their level of cognition and memory retention.
University of Pittsburgh Schools of the Health Sciences (2013, May 23). Drug reverses Alzheimer's disease deficits in mice.
By Lauren Horne
Scientists at Cambridge’s Department of Chemistry have been able to construct a detailed map that shows how the formation of proteins in the brain can lead to a build-up so massive that it can lead to the development of numerous brain-damaging diseases, chief among them is Alzheimer’s. In 2010, the Alzheimer’s Research Trust found that with dementia alone, it cost the UK economy E23 billion, way more than cancer and heart disease combined cost.
Normally, proteins are made up of chemical building blocks known as amino acids, which are joined together in a code ordered by our DNA. New proteins appear as long, thin strips, which are then intricately folded to properly carry out their designated biological function. However, there are points at which the protein can ‘misfold,’ or unfold and get tangled together with other newly-made proteins. The tangles stick to one another until they number in the millions, known as amyloid fibrils, and they start the huge deposits of proteins known as plaque, which are so huge that they are insoluble.
When the level of plaque in the brain reaches a critical level, a chain reaction is set off, and new focal points of tendrils form. From these tendrils, a smaller number of proteins, known as toxic oligomers, can easily diffuse through membranes, effectively killing neurons, causing memory loss, and other dementia symptoms.
This new groundbreaking information required scientists to come together, using kinetic experiments with a framework of theory. Master equations, more commonly used in the fields of chemistry and physics, aided researchers in their efforts to better understand a disease such as Alzheimer’s, and how better to fight it.
By Lauren Horne
University of Cambridge (2013, May 20). Molecular trigger for Alzheimer's disease identified. ScienceDaily. Retrieved May 22, 2013,
Samuel I. A. Cohen, Sara Linse, Leila M. Luheshi, Erik Hellstrand, Duncan A. White, Luke Rajah, Daniel E. Otzen, Michele Vendruscolo, Christopher M. Dobson, and Tuomas P. J. Knowles. Proliferation of amyloid-β42 aggregates occurs through a secondary nucleation mechanism. Proceedings of the National Academy of Sciences, 2013; DOI: 10.1073/pnas.1218402110
At Queen Mary University in London, researchers have conducted the largest study of genetic sequencing of human diseases known to date, identifying the genetic basis of six different diseases: autoimmune thyroid disease, celiac disease, Crohn’s disease, psoriasis, multiple sclerosis, and type 1 diabetes. For these diseases, the exact cause is not known, but according to the study, it was believed that the diseases were a complex combination of both genetic and environmental factors. For each disease, there was only a small portion of hereditability is explained by genetic variants.
In past studies and experiments, genetic variants were only identified as weak-effect. For this study, global scientists used highly throughput sequencing techniques in order to identify new variants, along with rarer and higher risk variants. In a previous experiment that contained twenty-five risk genes, the risk genes were found in a sample of nearly 42,000 individuals, 24,892 of the individuals with autoimmune disease, and 17,019 individuals were controls.
Within the May 2013 edition of the journal Nature, scientists suggest that the overall genetic risk of these diseases more than likely involves a complex combination of weak-effect variants which are common in the overall human population. David van Heel, Professor of Gastrointestinal Genetics at Barts and Queen Mary University, led the study, saying that there is a lesser risk of autoimmune disease from a few high-risk genetic variations, and a greater risk of random selection from the common genetic variants, each having a weak effect. Heel goes on to say that the genetic risk likely comes from inheriting a large amount of common variants from both parents. This would mean that it would be nearly impossible to test individually for such diseases. However, scientists are started to grasp the biological basis for the conditions that cause these diseases, opening a pathway for researchers to follow, hopefully leading to new drug avenues and possible treatment options.
By Lauren Horne
Queen Mary, University of London (2013, May 22). Largest genetic sequencing study of human disease. ScienceDaily. Retrieved May 23, 2013,
At Georgetown University Medical Center, tiny, almost meniscal dosage amounts of a Leukemia-inhibiting drug known as nilotinib, were being administered to lab mice in a clinical trial to see the effects of the drug on inhibiting the formation of certain proteins in the brain, which if allowed to proceed unchecked, would build up and cause any number of diseases, from Parkinson’s disease and even Alzheimer’s disease, to a lesser known disease known as Lewry body disease.
Neurologist and senior investigator for this study, Charbel E-H Moussa, MB and PhD, head of the dementia laboratory at Georgetown University stated that when this utilized drug, nilotinib, is used to treat CML, or chronic myelogenous leukemia. When used in high enough and safe doses, it causes the cancer cells to go into a state of autophagy, pushing them to cannibalize their own organelles, which leads to the death of tumor cells.
In the study that was performed, for the first time, cancer drugs were being utilized for a different cause. Mice in the lab that over-expressed a specific protein, known as alpha-Symuclein, were given one Milligram of nilotinib every two days. Previous testing of the drug concluded that it would get rid of the toxic protein found in the brain, the cells would go into a state of autophagy and within a matter of treatments, the lab mice treated with the drug had drastically better movement and functionality than the untreated mice.
At the end of the experiment, Moussa hypothesized that in order for therapy of these neurological diseases to be effective, it must happen as soon as possible. Later usage may result in retardation of further extracellular formation, as well as the accumulation of intracellular proteins such as Lewy bodies, which was the whole point of using the Leukemia drug in the first place.
Michaeline L. Hebron, Irina Lonskaya, and Charbel E.-H. Moussa. Nilotinib reverses loss of dopamine neurons and improves motor behavior via autophagic degradation of α-synuclein in Parkinson's disease models. Hum. Mol. Genet., May 10, 2013 DOI: 10.1093/hmg/ddt192
Georgetown University Medical Center (2013, May 10). Cancer drug prevents build-up of toxic brain protein. ScienceDaily.
From a recently published artilce in the May 2013 online issue of Neurology, a leading medical journal of the American Academy of Neurology, researchers in Minneapolis reported a study where 1,102 participants with average age of 79 years, were followed for the span of 3.7 years, were tested to see if ever they developed dementia. At the start of the study, 109 of the patients admitted to having skin cancer in the past. During the study trials, 32 people developed skin cancer, and 125 people developed dementia, including 100 people with Alzheimer’s dementia.
At the end of the testing period, of the 141 participants who developed skin cancer, only two of them also developed Alzheimer’s dementia. Resulting statistics showed that participants who developed skin cancer were around 80 percent less likely to develop Alzheimer’s disease versus those who did not develop skin cancer. There was no link found between Melanoma, a less common but powerful form of skin cancer, and Alzheimer’s disease. Nor was there a link with any other forms of dementia. The links were limited only to Alzheimer’s dementia and weaker forms of skin cancer.
Reviewing commentary of study author Richard B Lipton, MD, of Albert Einstein College of Medicine in Bronx, New York, stated that the protective effects of skin cancer were still unknown. However, there was a strong tendency to link physical activity protecting against dementia, and outdoor activities leading to a higher UV exposure from the sun, leading to a greater chance of skin cancer. Further insight guided Lipton to suggest genetic factors as a possible link between the two diseases, as the study showed that physical activity alone did not reduce the risk levels of Alzheimer’s to a meaningful level. More testing is surely needed, but this is a promising step in the right direction.
By Lauren Horne
R. S. White, R. B. Lipton, C. B. Hall, J. R. Steinerman. Nonmelanoma skin cancer is associated with reduced Alzheimer disease risk. Neurology, 2013; 80 (21): 1966 DOI: 10.1212/WNL.0b013e3182941990
American Academy of Neurology (AAN) (2013, May 15). Skin cancer may be linked to lower risk of Alzheimer's disease. ScienceDaily.
A new study by researchers at the Albert Einstein School of Medicine dramatically underscores the potential role of the NF-kB protein in aging. NF-kB is a master protein which controls many inflammatory chemicals throughout the body. Researchers at the Roskamp Institute have studied NF-kB for many years as a potential way of controlling chronic inflammation which accompanies aging and underlies conditions such as Alzheimer’s disease. This new study points to a part of the brain as regulating the aging process. The current view of aging generally suggests that enzymes, DNA, proteins and other constituents of the body essentially “wear out” with age, accumulating damage due to environmental insults until they no longer function properly. This new study suggests something quite different, namely that a part of the brain called the Hypothalamus deliberately induces aging throughout the body. It has been suggested that one reason why the brain might take such drastic action is to inhibit reproduction past a certain age. This suggestion is highly speculative at this stage, but the data offered by the Albert Einstein researchers suggests that, with age, increased NF-kB activity triggers degeneration in both the brain and other areas of the body. The researchers showed that as mice aged, they increasingly expressed NF-kB in the part of the brain that is normally responsible for the production of reproductive and growth hormones. The researchers artificially manipulated NF-kB activity using genetic techniques and showed that reducing NF-kB activity was associated with better performance in cognitive tests, greater muscle strength and greater bone mass and skin thickness. Conversely, exacerbation of NF-kB activity increased all of these peripheral signs of aging, as well as reducing cognitive abilities. Furthermore the research suggested that microglia (the inflammatory cells resident in the brain) are the originators of the NF-kB activity and this spreads to nearby neurons, including those responsible for growth and reproductive hormones. These findings are of direct significance to work at the Roskamp Institute as researchers there have shown that increased NF-kB collates strongly with Alzheimer’s pathology and pathology of other central nervous system disorders. Moreover, they have worked extensively on ways to reduce NF-kB activation, particularly using the naturally occurring compound Anatabine. Roskamp Institute researchers have shown in multiple preclinical studies of neuroinflammation (such as Alzheimer's, traumatic brain injury and Multiple Sclerosis) that Anatabine (supplied by RockCreek Pharmaceuticals) has potent anti-inflammatory properties. This new finding suggests that NFKB inhibitors might also have a role in decelerating aging. In fact, preliminary studies at the Roskamp Institute suggest that mortality in mice with Alzheimer pathology is reduced by Anatabine treatment. Additional studies are needed to clarify whether Anatabine might reduce the Hypothalamic inflammation and increase the release of hormones that oppose aging.
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