Recently discovered protein shows promise in treating Alzheimer’s diesease

New research in humans shows that the FKBP52 protein may prevent the Tau protein from turning pathogenic, or from causing disease.  

The FKBP52 protein was discovered by Baulieu 20 years ago in its ability to block Tau protein accumulation, which is commonly seen in Alzheimer’s disease (AD)patients. Microtubules are the railways in the brain upon which cellular cargo is transported. In patients with AD, tau tangles formed by misfolded tau proteins may compromise the stability of the microtubules within the nerve cells leaving them damaged. Currently, the mechanism of Tau toxicity is unclear and there are no drug treatments targeting Tau.

Professor Etienne Baulieu and colleagues at Inserm (National Institute for medical research in France) have recently published results that for the first time demonstrate that the FKBP52 protein may prevent hyperphosphorylation, or over accumulation of Tau protein, a characteristic of Alzheimer’s disease.

Specifically, the results of this study demonstrate a direct correlation between high levels of hyperphosphorylated Tau protein and reduced levels of FKBP52, in brain cells from patients that had died following AD, compared to normal brain cells. This indicates that when FKBP52 is reduced in nerve cells of AD patients, disease causing Tau is free to accumulate and contribute to the degeneration of brain cells.

IOS Press BV (2012, March 20). New hope for treating Alzheimer’s Disease: A Role for the FKBP52 protein. ScienceDaily. Retrieved April 5, 2012, from     
Julien Giustiniani, Marlène Sineus, Elodie Sardin, Omar Dounane, Maï Panchal, Véronique Sazdovitch, Charles Duyckaerts, Béatrice Chambraud, Etienne-Emile Baulieu. Decrease of the Immunophilin FKBP52 Accumulation in Human Brains of Alzheimer’s Disease and FTDP-17. Journal of Alzheimer’s Disease, Volume 29, issue 2 (March 2012) [link]


Are you sure that drink is “naturally” caffeinated?

Scientists discover companies labeling their synthetically caffeinated drinks as “natural”

Caffeine is one of the most important products in the United States, “America Runs on Dunkin’,” right? However, there are two kinds of caffeine – one proven to be more beneficial to human health than the other. Scientists from the University of Duisburg-Essen in Essen, Germany, have found the labeling of some “naturally caffeinated” drinks to be misleading. The study was published in Analytical Chemistry on February 17, 2012.

In caffeinated drinks there is one or both of two kinds of caffeine. There is naturally occurring caffeine, which actually has antioxidant benefits which may help to prevent heart disease and Alzheimer’s. Then, there is the caffeine which is added to energy drinks, juices, chocolates and sodas – this caffeine absorbs through the digestive system much faster than natural caffeine and can cause much more severe spikes and crashes resulting to difficulty sleeping, nervousness, heart palpitations or nausea.

Due to the differences in health effects, being able to discriminate between these two kinds of caffeine is important. However, the government requires “caffeine” to be listed on package labels but not which kind of caffeine. Dr. Maik A. Jochman and colleagues, with funding from the German Federal Ministry of Economics and Technology and the German Research Foundation, aspired to find a faster, simpler way to categorize caffeine’s origins.

Through the use of a technique called “stable-isotope analysis” they were able to differentiate between the kinds of caffeine (natural vs. synthetic) by using different kinds of carbon isotopes – variations of the same element – found in caffeine made by plants versus caffeine made in labs. The analysis took about 15 minutes and using it they were able to find four products that contained synthetic caffeine despite their claim to be “natural.”

Next time you might want to think twice about grabbing that “all natural” energy drink and go for a Fair-Trade coffee or tea – with possible health benefits and a guaranteed more gradual crash it seems to be the more enticing choice.


Original Study: “Caffeine in Your Drink: Natural or Synthetic?” Published in Analytical Chemistry on February 17, 2012.

Supporting Information: Ettinger, Jill. Organic Authority. “Need A Lift or A Jolt? Natural Vs. Synthetic Caffeine.”

New brain-imaging technique can predict who will suffer from Alzheimer’s and accelerate research


These are baseline and follow-up brain scans of a patient who converted to Alzheimer's disease after two years (images to right of white line) that shows high medial temporal binding at baseline (lower left) and follow-up (lower right), but also demonstrates more baseline binding in frontal (upper images) and lateral temporal regions. Warmer colors (yellows, reds indicate higher binding levels. A second patient did not convert to Alzheimer's after two years (images to left of white line) showing medial temporal (lower scans), but very mild frontal (upper scans) binding at baseline and follow-up. (Credit: UCLA)

Brain degeneration associated with the loss of memory and other cognitive functions currently affects millions of adults, and this number will only increase as the baby boomer generation continues to age. Today, almost 20 percent of the population that is 65 or older suffers from mild cognitive impairment (MCI) and 10 percent have diagnosable dementia.

Researchers from UCLA report in the February issue of the journal Archives of Neurology that the brain-imaging technique they had previously reported as being a possible assessment tool for measuring neurological changes associated with dementia and Alzheimer’s disease has produced promising results.

The UCLA team created a chemical marker called FDDNP that binds to both plaque and tangle deposits – hallmarks of Alzheimer’s disease (AD) – which can then be viewed using a positron emission tomography (PET) brain scan. This technique essentially provides researchers with a “window into the brain” allowing them to pinpoint where in the brain these abnormal structures are developing.

Further, they are “finding that this may be a useful neuro-imaging marker that can detect changes early, before symptoms appear, and it may be helpful in tracking changes in the brain over time,” said Dr. Gary Small, a member of this UCLA lab team.

The study, reported in February, assessed 43 participants who, at the start of the 2-year study, did not have dementia. Participants had an average age of 64 years and about half of the participants (22) had normal aging and the other half (21) had mild cognitive impairment (MCI), a condition that increases a person’s risk of developing AD. The results showed that for both groups, FDDNP binding had increased in the brain and that this was associated with progression of cognitive decline.

For the patients with MCI at the start of the study, the level of initial binding provided the greatest accuracy in identifying those who developed AD after two years. Specifically, six of the 21 participants in the MCI group were diagnosed with AD at the 2-year follow-up. Similarly, for patients in the normal aging group, three of the 22 participants developed MCI at the follow-up and two of these three participants had the highest initial baseline FDDNP values.

The next steps for this research are examining changes over a longer period of time with a larger sample and also using this labeling/imaging technique to track the effectiveness of clinical interventions for brain aging. More specifically, the UCLA lab team will be tracking the effectiveness of a high potency form of curcumin – a recently FDA approved spice with anti-amyloid, anti-tau and anti-inflammatory properties – that can prevent the accumulation of the plaques and tangles that are hallmarks of AD.

The discovery of new imaging techniques that allow scientists to monitor changes in the AD brain is extremely exciting. Prior to these techniques, researchers were only able to examine the pathology of AD in post-mortem brains. These imaging techniques allow researchers to monitor the development of AD in real-time and can prove to be very useful in accelerating drug discovery efforts.


G. W. Small, P. Siddarth, V. Kepe, L. M. Ercoli, A. C. Burggren, S. Y. Bookheimer, K. J. Miller, J. Kim, H. Lavretsky, S.- C. Huang, J. R. Barrio. Prediction of Cognitive Decline by Positron Emission Tomography of Brain Amyloid and Tau. Archives of Neurology, 2012; 69 (2): 215. Link to article
University of California, Los Angeles (UCLA), Health Sciences (2012, February 13). Brain-imaging technique predicts who will suffer cognitive decline over time. ScienceDaily. Retrieved March 1, 2012, from


Could it be? A Drug that Cures Cancer and Alzheimer’s disease?

Amyloid beta (red areas-left image) peptides clear from the brain of an Alzheimer's mouse after three days of treatment with a cancer drug (right image). Souce: AAAS/Science

Neuroscientists at Case Western Reserve University School of Medicine have just reported a breakthrough in their efforts to find a cure for Alzheimer’s disease (AD). The findings, published in the journal of Science, show that the administration of a drug in mice appears to quickly reverse the pathological, cognitive, and memory deficits caused by the onset of AD.

The drug with this potential: Bexarotene. Bexarotene has been FDA approved for the treatment of a type of skin cancer for more than a decade. The Landreth lab at Case Western explored whether this medication would also be useful in treating patients with Alzheimer’s disease. The results the lab obtained were more than promising.

Before I delve into their findings, it is important to understand basic AD pathology. AD arises in large part from the body’s inability to clear naturally-occurring beta amyloid from the brain. In 2008, members of the Landreth lab discovered that the main cholesterol carrier in the brain, Apolipoprotein E (ApoE), facilitated the clearance of the amyloid beta proteins. So, they decided to explore the effectiveness of bexarotene for increasing ApoE expression. This was based off the idea that elevation of ApoE levels speeds the clearance of amyloid beta from the brain and bexarotene acts by stimulating the receptors which control how much ApoE is produced.

The researchers were stunned by the speed with which bexarotene improved memory deficits and behavior even as it also acted to reverse the pathology of AD. Today, the scientific community agrees that small soluble forms of amyloid beta cause the memory impairments displayed by animal models and humans with the disease. Within just six hours of administering bexarotene, however, soluble amyloid levels fell by 25 percent. Even more astonishing was the fact that the effect lasted three days and was correlated with rapid improvement in a broad range of behaviors in three different mouse models of AD.

Researchers found that more than half of the plaques had been cleared within 72 hours. Ultimately, the reductions totaled 75 percent. The research team believes that the bexarotene reprogrammed the brain’s immune system to “eat” the amyloid deposit which demonstrates that the drug addresses the amount of both soluble and deposited forms of amyloid beta within the brain and thus, reverses the pathological features of the disease in mice.

This study also identifies a link between the primary genetic risk factor for AD and a potential therapy to address it. Humans have three forms of ApoE: ApoE2, ApoE3, and ApoE4. Carriers of the ApoE4 gene are at an increased risk for developing Alzheimer’s. The Landreth lab has previously shown that the e4 variant was impaired in its ability to clear amyloid. These new results suggest that elevation of ApoE levels may be an effective strategy to clear the forms of amyloid associated with impaired memory and cognition.

The Landreth lab is in the very early stages of beginning the translation to clinical trials of the drug. One can only hope that this drug has some effect on amyloid clearance in humans similar to that seen in the mouse models.

It is important to note that while this study appears to be a dramatic breakthrough in the efforts for finding a cure for AD, the results were only found in mouse models of the disease. There have been 300 reports of treatments that cure Alzheimer’s in mice since 1995. Unfortunately the number of cures in humans in 2012 still reads zero. This is because while the mouse model holds genetic mutations that cause mice to display similar cognitive impairments, it is an imperfect model for a true AD patient. No single mouse replicates all the symptoms associated with human Alzheimer’s disease. The exact cause and progression of AD remains unknown, which makes finding a cure difficult when we still haven’t even unwrapped the actual problem. Lastly, if this drug were to be effective in humans, it still would not help the patients in the advanced stages of Alzheimer’s, whose memory loss and impaired cognitive abilities are the result of neuronal death. Bexarotene can reduce levels of amyloid beta, but unfortunately it cannot reverse cell death.

Point being, while these new results hold promise for the future of AD, we must not forget that there is much more to be discovered about the cause and progression of this terrible disease.

Resource:  Cramer, et al. ApoE-Directed Therapeutics Rapidly Clear Beta-Amyloid and Reverse Deficits in AD Mouse Models. Science (9 February 2012) DOI: 10.1126/science.1217697 

One small step for Alzheimer’s research; one giant leap for mankind

In this image, DNA is shown in blue, dendrites and cell bodies in red and endosomal markers Rab5 and EEA1 in green and orange, respectively. (Credit: UC San Diego School of Medicine)


Scientists have recently created, for the first time, Alzheimer’s neurons from induced pluripotent stem cells. These stem-cell derived neurons, made from patients with Alzheimer’s disease, provide researchers with a novel tool for unraveling the mechanisms underlying this much-dreaded disorder. “Creating highly purified and functional human Alzheimer’s neurons in a dish – this had never been done before,” reports senior study author Lawrence Goldstein, PhD of the UC San Diego Stem Cell Program.

Until now, “researchers have had to work around, mimicking some aspects of the disease in non-neuronal human cells or using limited animal models. Neither approach is really satisfactory,” said Goldstein. Now, the living cells can provide a new method for studying the cause of AD and an unprecedented tool for developing and testing drugs to treat the disorder.

The findings by Goldstein and colleagues were published in the January 25 online edition of the journal Nature. Here the authors explain that they extracted primary fibroblasts from the skin tissues of two patients with familial AD (early-onset form with a genetic predisposition), two patients with sporadic AD (cause unknown) and two other subjects with no known neurological problems. They were then able to reprogram the fibroblasts of the AD patients into iPSCs that then differentiated into working neurons.

The iPSCs-derived neurons not only exhibited normal electrophysiological activity and formed functional synaptic contacts, but most importantly they possessed higher-than-normal levels of proteins associated with AD. These abnormally high levels of specific proteins are tell-tale indicators of the disorder.

Today, there are an estimated 5.4 million Americans that have Alzheimer’s disease and this number is believed to grow to 16 million by 2050. In 2011 alone, the cost of caring for AD patients was more than $183 billion, projected to reach $1.1 trillion by 2050. AD is the sixth leading cause of death in the United States, killing more than 75,000 Americans annually. Currently, there are no drugs to prevent, alter, or cure the disease. Goldstein emphasized the opportunity that iPSC-derived Alzheimer’s neurons present, “At the end of the day, we need to use cells like these to better understand Alzheimer’s and find drugs to treat it. We need to do everything we can because the cost of this disease is just too heavy and horrible to contemplate. Without solutions, it will bankrupt us – emotionally and financially.”



Mason A. Israel, Shauna H. Yuan, Cedric Bardy, Sol M. Reyna, Yangling Mu, Cheryl Herrera, Michael P. Hefferan, Sebastiaan Van Gorp, Kristopher L. Nazor, Francesca S. Boscolo, Christian T. Carson, Louise C. Laurent, Martin Marsala, Fred H. Gage, Anne M. Remes, Edward H. Koo, Lawrence S. B. Goldstein. Probing sporadic and familial Alzheimer’s disease using induced pluripotent stem cells. Nature, 2012; DOI: 10.1038/nature10821
University of California, San Diego Health Sciences. “Alzheimer’s neurons from pluripotent stem cells: First-ever feat provides new method to understand cause of disease, develop drugs.” ScienceDaily, 25 Jan. 2012. Web. 2 Feb. 2012.