New Antibody Drug Clears Brain of Amyloid Plaques and Delays Onset of Alzheimer’s Disease Symptoms in Small Clinical Trial


An experimental drug called aducanumab seem to be able to remove the toxic proteins that build up and cause the onset of Alzheimer’s disease in the brain, according to findings from a small clinical trial. Because of the small size of this trial, I must stress that these results, though potentially exciting, should also elicit some caution.

The results of this small clinical trial were reported in the journal Nature on August, 31, 2016. In this trial, aducanumab dissolved amyloid-β proteins in patients suffering from early-stage Alzheimer’s disease. This was a Phase I clinical trial, and therefore, was designed mainly to test the safety of aducanumab in human patients. Thus, the final word on whether aducanumab works to mitigate the memory losses and cognitive decline associated with Alzheimer’s disease must be subjected to clinical trials specifically designed to test such things. Two larger phase III trials are presently in progress, and are planned to be completed approximately in 2020 (note: this is an estimate).

The latest study enrolled 165 subjects who were split into different groups; subjects in one group received aducanumab and subjects in the other group were administered a placebo. In the group that received aducanumab infusions, 103 patients were given the drug once a month for up to 54 weeks. These patients experienced a reduction in the amount of tangled amyloid-β in their brains. These clinical recapitulated the results of pre-clinical experiments in laboratory mice that were actually reported in the same paper. Aducanumab seems to clear amyloid-β plaques from the brains of laboratory mice and human patients.

“This drug had a more profound effect in reversing amyloid-plaque burden than we have seen to date,” says psychiatrist Eric Reiman, who serves as executive director of the Banner Alzheimer’s Institute in Phoenix, Arizona. Reiman and his colleagues are in the process of testing other approaches for Alzheimer’s prevention and treatment. “That is a very striking and encouraging finding and a major advance.” Reiman wrote a commentary accompanying the article.

“This is the best news we’ve had in my 25 years of doing Alzheimer’s research, and it brings hope to patients and families affected by the disease,” says neurologist Stephen Salloway of Butler Hospital in Providence, Rhode Island, who is a member of the clinical team that ran the trial.

Patients in those groups that received aducanumab were divided into different subgroups that were given one of four different doses. Those patients who received the highest doses also had the highest reductions in plaques, and a group of 91 patients who had been treated for 54 weeks saw slower cognitive declines than did those who received placebo infusions.

Neuroscientists have had a long-standing and often spirited debate over the significance of the accumulation of amyloid-β in the pathology of Alzheimer’s disease. The memory loss and other symptoms of Alzheimer’s disease almost certainly result from the die-off of neurons in the brain, but do the amyloid-β plaques form as a consequence of this massive neuronal die-off or are they the cause of it? This clinical trial seems to provide good evidence for the “amyloid hypothesis,” since the elimination of amyloid-β protein seems to ameliorate the symptoms of Alzheimer’s disease.

Reiman however, cautions, wisely I think, that this trial is too small to definitively demonstrate that aducanumab actually works. Several other drugs for Alzheimer’s disease have shown promising results in the early-stage of clinical trials only to end in failure, and even in the deaths of patients.

Aducanumab led to abnormalities on brain-imaging scans in less than one-third of the patients. Researchers must closely monitor these anomalies in Alzheimer’s trials, because some participants in previous Alzheimer’s antibody trials have died as a result of brain inflammation. Fortunately, all of the reported imaging abnormalities eventually disappeared in about 4 to 12 weeks, and none of the patients who showed such abnormalities were hospitalized. Curiously, some of the patients who showed imaging anomalies continued to take the drug despite these side effects. Patients who received higher doses of the drug, or who had genetic risk factors for Alzheimer’s, were more likely to develop the brain anomalies.

Biogen, the company that makes aducanumab, has adjusted the drug’s dosage and the monitoring schedule for patients who have an increased genetic risk for Alzheimer’s in its phase 3 trials. According to Reiman, drug makers, like Biogen, must determine if a particular dosage that hits a “sweet spot” that is strong enough to work without causing potentially lethal brain inflammation.

Aducanumab is a bright spot in the field of Alzheimer’s therapeutics after years of failed antibodies and other types of drug trials. The antibody drug solanezumab failed to slow cognitive decline in two large 2013 clinical trials.  However solanezumab may have a second life and is being tested in multiple other trials, one of which includes individuals with mild Alzheimer’s disease. Results from this trial might be reported as early as the end of 2016.

Other therapeutic strategies undergoing clinical trials include strategies that target enzymes called β-secretase 1 that processes amyloid proteins, antibodies that attack the so-called the microtubule-binding tau protein, which is found in high concentrations in the neurofibrillary tangles found in the brains of many Alzheimer’s disease patients.

“The fact that we now have an antibody that gets into the brain sufficiently enough to engage its target and remove plaques is an important development, and we look forward to seeing results from this and other phase 3 trials,” Reiman says.

First Stem Cell Trial for Alzheimer’s Disease Will Enroll Patients Next Year


A research group from the University of Miami Miller School of Medicine will be conducting the first clinical trial that will test the ability of stem cells to treat Alzheimer’s disease.

According the Bernard Baumel, assistant professor of neurology at the Miller School of Medicine and the principal investigator for this phase I clinical trial, said “We believe infusions of these types of stem cells have the potential to be beneficial to individuals with Alzheimer’s disease.” Because this trial is a phase 1 clinical trial, it will test the safety of this treatment strategy.

Baumel and his colleagues plan to test the safety of mesenchymal stem cells (MSCs) as a treatment for Alzheimer’s disease.  In order to acquire high-quality MSCs for this clinical trials, Dr. Baumel is collaborating with his colleague Joshua Hare, Louis Lemberg Professor of Medicine and director of the Miller School’s Interdisciplinary Stem Cell Institute (ISCI).  Dr. Hare is an expert in the use and manipulation of MSCs who has developed a life sciences company called Longeveron that isolates, characterized and stores MSCs for clinical applications.

“Stem cells are very potent anti-inflammatories,” Dr. Baumel said. “Because the amyloid plaques found in the brains of Alzheimer’s disease patients are associated with inflammation, infusions of stem cells may help to improve or stabilize that condition. Those new brain cells may then be able to replace damaged cells in Alzheimer’s patients.”

Previous work in several different laboratories has demonstrated the anti-inflammatory capacities of MSCs (Chen PM, et al J Biomed Sci. 2011; 18:49), but other laboratories have even observed that, under certain conditions, MSCs can differentiate into brain cells (Tsz Kin Ng, et al World J Stem Cells. 2014 Apr 26; 6(2): 111–119). Therefore, MSCs potentially provide a powerful one-two punch for treating Alzheimer’s disease patients.

This clinical trial is called “Allogeneic Human Mesenchymal Stem Cell Infusion Versus Placebo in Patients with Alzheimer’s Disease,” and enrollment for this trial will begin in early 2016 and continue through to 2018. Patients enrolled in the study will have their undergo cognitive function tests before and after the treatment, quality of life assessments and brain volume measurements in order to acquire some knowledge of the potential effectiveness of this cell-based treatment strategy.

Patients with mild Alzheimer’s disease but who are otherwise healthy will be encouraged to enroll in this study.

Cord Blood Cells As a Potential Treatment for Alzheimer’s Disease


Jared Ehrhart from the University of South Florida, who also serves as the Director of Research and Development at Saneron CCEL Therapeutics Inc, and his coworkers have shown that cells from umbilical cord blood can not only improve the health of mice that have an experimental form of Alzheimer’s disease (AD), but these can also be administered intravenously, which is safer and easier than other more invasive procedures.

Laboratory mice can be engineered to harbor mutations that can cause a neurodegenerative disease that greatly resembles human AD. One such mouse is the PSAPP mouse that harbors two mutations that are known to cause an inherited, early-onset form of AD in humans. By placing both mutations in the same mouse, the animal forms the characteristic protein plaques more rapidly and shows significant AD symptoms and brain pathology.

Ehrhart used PSAPP mice to test the ability of human umbilical cord blood to ameliorate the symptoms of AD. He injected one million Human Umbilical Cord Blood Cells (HUCBCs) into the tail veins of PSAPP mice and 2.2 million into the tail veins of Sprague-Dawley rats. Then he harvested their tissues at 24 hours, 7 days, and 30 days after injection. Then Ehrhart and his team used a variety of techniques to detect the presence of the HUCBCs.

Interestingly, the HUCBCs were able to cross the blood-brain barrier and take up residence in the brain. The cells remained in the brain and survived there for up to 30 days and did not promote the growth of any tumors.

Several studies have shown that the administration of HUCBCs to mice with a laboratory form of AD can improve the cognitive abilities of those mice (see Darlington D, et al., Cell Transplant. 2015;24(11):2237-50; Banik A, et al., Behav Brain Res. 2015 Sep 15;291:46-59; Darlington D, et al., Stem Cells Dev. 2013 Feb 1;22(3):412-21). However, in such cases it is essential to establish that the administered cells actually found their way to the site of damage and exerted a regenerative response.

Even though Ehrhart and his troop found that the intravenously administered HUCBCs were widely distributed throughout the bodies of the animals, they persisted in the central nervous system for up to one month after they were injected. In the words of this publication, which appeared in Cell Transplantation, the HUCBCs were “broadly detected in both in the brain and several peripheral organs, including the liver, kidneys, and bone marrow.”. The fact that such a minimally invasive procedure like intravenous injection can effectively introduce these cells into the bodies of the PSAPP mice and still produce a significant therapeutic effect is a significant discovery.

Ehrhart and his colleagues concluded that HUCBCs might provide therapeutic effects by modulating the inflammation that tends to accompany the onset of AD. Furthermore, these cells do not need to be delivered by means of an invasive procedure like intracerebroventricular injection. Furthermore, even though HUCBCs were detected in other organs, their numbers in those places was not excessive and the ability of the HUCBCs to cross the blood-brain barrier suggests that these cells might serve as safe, effective therapeutic agents for AD patients some day.

Gene Therapy for Stroke Applied with Eye Drops


Administering growth factors to the brains of patients with neurodegenerative diseases can prevent neurons from dying and maintain the structure of their brains. For example, a recently published clinical trial by Nagahara and others from the Department of Neuroscience and the University of California, San Diego examined 10 Alzheimer’s disease (AD) patients and showed that these patients responded to Nerve Growth Factor gene therapy. When they compared treated and nontreated sides of the brain in 3 patients who underwent gene transfer, expansion of cholinergic neurons was observed on the NGF-treated side. Both neurons exhibiting the typical pathology of AD and neurons free of such pathology expressed NGF, which indicates that degenerating cells can be infected with therapeutic genes. No adverse pathological effects related to NGF were observed. In the words of this study, “These findings indicate that neurons of the degenerating brain retain the ability to respond to growth factors with axonal sprouting, cell hypertrophy, and activation of functional markers. [Neuronal s]prouting induced by NGF persists for 10 years after gene transfer. Growth factor therapy appears safe over extended periods and merits continued testing as a means of treating neurodegenerative disorders.” See JAMA Neurol. 2015 Oct 1;72(10):1139-47.

Another study that also shows that the brains of AD patients can respond to growth factors comes from a paper by Ferreira and others from the Journal of Alzheimers Disease. These authors hail from the Karolinska Institutet, Stockholm, Sweden, and they implanted encapsulated NGF-delivery systems into the brains of AD patients. Six AD patients received the treatment during twelve months. These patients were classified as responders and non-responders according to their twelve-month change in the Mini-Mental State Examination (MMSE), which is a standard. In order to set a proper standard of MMSE decline and brain atrophy in AD patients, Ferreira and other examined 131 AD patients for longitudinal changes in MMSE and brain atrophy. When these results provided a baseline, the NGF-treated were then compared with these baseline data. Those patients who did not respond to the implanted NGF showed more brain atrophy, and neuronal degeneration as evidenced by higher CSF levels of T-tau and neurofilaments than responding patients. The responders showed better clinical status and less pathological levels of cerebrospinal fluid (CSF) Aβ1-42, and less brain shrinkage and better progression in the clinical variables and CSF biomarkers. In particular, two responders showed less brain shrinkage than what was normally experienced in the baseline data. From these experiments, Ferreira and others concluded that encapsulated biodelivery of NGF might have the potential to become a new treatment strategy for AD.

Now new, even simpler treatment strategy has been developed by a research team funded by the National Institute of Biomedical Imaging and Bioengineering for delivering gene therapy to the brains of AD patients. This team invented an eye drop cocktail that can deliver the gene for a growth factor called granulocyte colony stimulating factor (G-CSF) to the brain. They have tested these eye drops on mice with stroke-like injuries.

When treated with these eye drops, the mice experienced a significant reduction in shrinkage of the brain, neurological defects, and death. Ingeniously, this research group also devised a way to use Magnetic Imaging Systems to monitor how well the gene delivery worked. This one-two punch of an inexpensive and noninvasive delivery system combined with a monitoring technique that is equally noninvasive might have the ability to improve gene therapy studies in laboratory animals. Such a strategy might also be transferable to human patients. Imagine that acute brain injury might be treatable in the near future by emergency medical workers by means of eye drops that carry a therapeutic gene.

The growth factor G-CSF (granulocyte-colony stimulating factor) has more than proven itself in several animal studies. In model systems for stroke, AD, and Parkinson’s disease, G-CSF promotes neuronal survival and decreases inflammation (See McCollum M, et al., Mol Neurobiol. 2010 Jun;41(2-3):410-9; Frank T, et al., Brain. 2012 Jun;135(Pt 6):1914-25; Prakash A, Medhi B, Chopra K. Pharmacol Biochem Behav. 2013 Sep;110:46-57; Theoret JK, et al., Eur J Neurosci. 2015 Oct 16. doi: 10.1111/ejn.13105). Unfortunately, when G-CSF was when tested in a human trial in more than 400 stroke patients, it failed to improve neurological outcomes in stroke patients. Therefore, it is fair to say that the excitement this growth factor once generated is not what is used to be. A caveat with this clinical trial, however, is that G-CSF expression in the brains of these patients might have been rather poor in comparison to the expression achieved in mice. To properly establish the efficacy or lack of efficacy of gene therapies in human patients, scientists MUST convincingly determine that the gene is expressed in the target tissue of test subjects. This has been a perennial problem that has dogged many gene therapy trials.

Philip K. Liu, Ph.D., of the Martinos Center for Biomedical Imaging at Harvard Medical School, and his collaborators, H. Prentice and J. Wu of Florida Atlantic University, developed the novel MRI-based techniques for monitoring G-CSF treatment and the eye drop-based delivery system as well. MRI can efficiently confirm successful administration and expression of G-CSF in the brain after gene therapy delivery. This work was published in the July issue of the journal Gene Therapy.

“This new, rapid, non-invasive administration and evaluation of gene therapy has the potential to be successfully translated to humans,” says Richard Conroy, Ph.D., Director of the NIBIB Division of Applied Science and Technology. “The use of MRI to specifically image and verify gene expression, now gives us a clearer picture of how effective the gene therapy is. The dramatic reduction in brain atrophy in mice, if verified in humans, could lead to highly effective emergency treatments for stroke and other diseases that often cause brain damage such as heart attack.”

Liu’s motivation for this project was to develop a gene delivery method that was simple, and could rapidly and effectively deliver the genes to the brain. A simple gene delivery technique would obviate the need for highly trained staff and expensive, sophisticated equipment. They also sought to successfully demonstrate the efficacy of their technology in laboratory animals so that it could be translated to humans.

To test their system, they deprived mice of blood flow to their brains, and then administered a genetically-engineered adenovirus that had the G-CSF gene inserted into its genome. This particular adenovirus is known to be quite safe in humans and can also efficiently infect brain cells. The adenovirus was also safely and effectively administered through eye drops. The simplicity of the eye drops means that it is easy to give multiple gene therapy treatments. By delivering the G-CSF gene at multiple time points after the induced blockage, Liu and others found that the treated mice showed significant reductions in deaths, brain atrophy, and neurological deficits as measured by behavioral testing of these mice.

MRI examinations also confirmed that G-CSF was expressed in treated mouse brains. Liu and his group used an MRI contrast agent tethered to a segment of DNA that targets the G-CSF gene. This inventive strategy enabled MRI imaging of G-CSF gene expression in mouse brains. The brains of mice treated with the recombinant adenovirus showed significant expression of the G-CSF gene. Control mice treated with the same adenovirus carrying the contrast agent bound to a different piece of DNA produced no MRI signal in the brain.

Control mice that did not receive G-CSF in eye drops, MRI scan identified areas of the brain with reduced metabolic activity and shrinkage as a result of the stroke. Mice treated with the G-CSF gene therapy, however, kept their usual levels of metabolic activity and did not have any evidence of brain atrophy. On average, after a stroke, mouse brain striatum size decreased more than 3-fold, from 15 square millimeters in normal mice to less than 5 square millimeters. But in contrast, G-CSF-treated mice retained an average striatum volume of more than 13 square millimeters, which is close to normal brain volume.

“We are very excited about the potential of this system for eventual use in the clinic,” says Liu, “The eye drop administration allows us to do additional treatments with ease when necessary. The MRI allows us to track gene expression and treatment success over time. The fact that both methods are non-invasive increases the ability to develop, and successfully test gene therapy treatments in humans.”

Liu and his collaborators are now jumping through the multitudes of hoops to take this work to a clinical trial. They are trying to secure FDA approval for the use of the G-CSF gene therapy in human patients. Finally, they also need to invite collaborating with physicians to develop their clinical trial protocol.

Abnormal Lipid Metabolism Suppresses Adult Neural Stem Cell Proliferation in an Animal Model of Alzheimer’s Disease


The brain is deeply dependent on lipid (fatty molecule) metabolism for proper development and function. Could abnormal lipid metabolism affect the brain’s stem cell population? Oh yes.

Karl J.L. Fernandez and his coworkers from the Research Center of the University of Montreal Hospital in Montreal, Canada and other collaborators has shown that neural stem cell populations in the brain can be compromised by abnormal lipid metabolism and that such abnormalities are characteristic of Alzheimer’s disease.

3xTg-AD mice form plaques in their brains that are similar to those in the brains of Alzheimer’s disease patients. Fernandez and his colleagues discovered that 3xTg-AD mice accumulate lipids within ependymal cells, which line the ventricles of the brain and serve as the main support cell of the forebrain Neural Stem Cells (NSCs). Interestingly, brains from Alzheimer’s disease patients, when examined after death also showed the accumulation of lipids within the same cell population.

Fernandes_graphicalabstact

When these lipids were examined further, it was clear that they were oleic acid-enriched fats (oleic acid is found in olive oil). In fact, injecting oleic acid into this area of the brain could recapitulate this pathology. When Fernandez and others inhibited oleic acid synthesis, they were able to fix the stem cell issues in the 3xTg-AD mice.

This fascinating study shows that the pathology in Alzheimer’s disease might be caused by perturbation of fatty acid metabolism in the stem cell niche that suppresses the regenerative functions of NSCs. Preventing accumulation of these fats in the cells surrounding the NSC population can potentially fix the stem cell abnormalities in patients with Alzheimer’s disease.

This study was published in the journal Cell Stem Cell.

Society for Neuroscience Conference 2014 Continued


Let me emphasize that the huge number of posters and talks at the SfN conference made it impossible to attend all of them, so my recollections here are some of the high points that I was able to take in. There is a lot of terrific science going on out there and these conferences are windows into it.

One poster described a feeding study in rats. One group of rats received a diet rich in omega-3 fatty acids, which are found in fish oils and soy. Another group was fed a standard laboratory diet that tends to skim on the omega-3 fatty acids. In the brains of the omega-3-fed rats, the expression off the gene that encodes Brain Derived Neurotropic Factor or BDNF increased significantly.

This is significant because BDNF promotes the survival of nerve cells (neurons) by playing a role in the growth, maturation (differentiation), and maintenance of these cells. In the brain, BDNF protein is active at the connections between nerve cells (synapses), where cell-to-cell communication occurs. The synapses can change and adapt over time in response to experience, a characteristic called synaptic plasticity, and BDNF regulates synaptic plasticity, which is important for learning and memory.

When these researchers examined why the BDNF gene was unregulated in rats fed the omega-3-rich diet, they discovered that the starting point of the gene, which is called the promoter was nice and clear. In the standard diet rats, the promoter of the BDNF gene was chemically modified with methyl (-CH3) groups. In the absence of the methyl groups, the transcription factor CTCF was able to bind and increase the rate of transcription. If the promoter was chemically modified with methyl groups, then a protein called MeCP2 bound to the promoter and prevented expression of BDNF.

This group looked further and discovered that the omega-3-rich diet seemed to influence the expression of BDNF by means of the balance of reduced and oxidized versions of electron carriers in cells, in particular, the ratio of NAD+ to NADH. NAD is a major electron carrier in cells and the ratio of NAD+, the oxidized version of this molecule, to the reduced version of this molecule, NADH, is a measure of the energy charge of the cell and how well-fed the individual is. More importantly, NAD is a substrate for another regulator of gene expression called Sirtuins.

Sirtuins are protein deacetylases, but they are unusual deacetylases since many of them they do not simply hydrolyze acetyl-lysine residues. Instead they couple lysine deacetylation to NAD hydrolysis. This hydrolysis produces O-acetyl-ADP-ribose, which is the deacetylated substrate and nicotinamide, which is an inhibitor of sirtuin activity. The dependence of sirtuins on NAD links their enzymatic activity directly to the energy status of the cell via the cellular NAD:NADH ratio.

The fact that a diet high in omega-3 fatty acids affects the NAD/NADH ratio is significant for Alzheimer’s disease because the sirtuin, SIRT1, deacetylates and coactivates the promoter for the gene that encodes the retinoic acid receptor beta gene, which subsequently upregulates the expression of alpha-secretase (ADAM10). Alpha-secretase is able to suppress beta-amyloid production. ADAM10 activation by SIRT1 also induces the Notch signaling pathway, which is known to repair neuronal damage in the brain. All of this begins with a dietary factor that actually protects the brain from Alzheimer’s disease by profound changes in gene expression.

Another poster from an Italian group used the 5XFAD mouse model of Alzheimer’s disease to test a growth factor called “painless Nerve Growth Factor” on mice with protein plaque formation in their brains. The growth factor was given by placing droplets of the growth factor in the noses of the mice while they were anesthetized. The results were stunning. Normally, 5XFAD mice get plaques quickly in their brains and lots of them. However, the growth factor was able to rescue the onset of behavioral deficits and reduces, although not eliminate, plaque formation. Other brain-specific pathologies found in these mice were reduced, such as astrocytosis. The wandering white cells in the brain known as microglia did a better job of gobbling up protein aggregates and clearing them from the brain, and the markers of inflammation were significantly reduced. I asked the investigator if there were plans to try to move this to clinical trials, and she said that she was unable to do so because of a lack of funding. Maybe someone will collaborate with this dear lady to make it so?

In another poster, the overexpression of an enzyme called heparanase in the brain decreased the burden of protein aggregates in the brains of mice with Alzheimer’s disease. I was not able to get into the details of this poster because of time.

In another poster, a very energetic young man told me about his very interesting work with a Parkinson’s disease model in rodents. If mice are administered a drug called MPTP (short for 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), the dopamine-using neurons in the brain will specifically take up this drug in high concentrations and it will kill them. Therefore, this drug is an excellent model system to study Parkinson’s disease in mice.

Prokineticin-2 is a gene that is expressed in high quantities in the surviving dopamine-using neurons that came from the brains of Parkinson’s disease patients after their deaths. When Prokineticin-2 was overexpressed in cultured dopaminergic neurons, they unregulated a protein called Bcl-2. Bcl-2 is one of the group of proteins can protect cells from dying. Therefore, Prokineticin-2 is a prosurvival protein.

Next, this chap switched from a culture system to a “in a living animal” system or an in vivo system. By using genetically engineered viruses that overexpressed Prokineticin-2 in the brains of mice, he discovered that this viruses did not adversely affect the mice and he did in fact achieve high levels of Prokineticin-2 in the brains of mice with this recombinant viruses. The overexpression did not affect the mice in the least. When he did the same experiment with MPTP-treated mice – oh, just to be clear, he overexpressed Prokineticin-2 first and then administered the MPTP because it takes about 30 days for the viruses to properly upregulate Prokineticin-2 – he saw decreased inflammation in the brain, and increase in Bcl-2 and Pink1 expression in the brain (both of these genes are pro-survival genes), and the behavioral problems of the mice never emerged with the severity of the MPTP mice. When he examined TH – an enzyme that makes the neurotransmitter dopamine, he saw that levels of this enzyme were up too. This means that the dopamine-using neurons were surviving. Is this cool stuff or what?

That’s enough for now. More later.

Fat-Based Stem Cells Support New Brain Cell Growth in Alzheimer’s Disease Mice


Alzheimer’s disease (AD) causes progressive death of brain cells and dementia. The loss of memory, coordination, and eventually motor function is relentless and horrific, and causes extensive suffering, financial pressures and loss. Stem cell treatments have been proposed as a treatment for AD, but such treatments have met resistance because of the complex pathology of AD. Introducing new neurons into the brain will do little good if cells are normally dying. However, some work with laboratory animals has suggested that stem cell treatments can benefit animals with conditions that approximately AD (see Kim S, et al., PLoS One. 2012;7(9):e45757; Bae JS, et al., Curr Alzheimer Res. 2013 Jun;10(5):524-31). However there are few studies that examine the therapeutic effect of mesenchymal stem cells from fat tissue or “adipose-derived stem cells” on mice with AD, and the effect of these cells on the oxidative injury that tends to accompany AD, and if these stem cells stimulate the generation of new neurons in the brains of AD mice.

Now we have evidence that transplantation of mesenchymal stem cells can stimulate for formation of new brain cells in adult rat or mouse models of AD and improve tissue structure and function after a stroke. Dr. Yufang Yan and her team from the School of Life Sciences at Tsinghua University, China transplanted adipose-derived stromal cells (ADSCs) into a part of the brain known as the hippocampus of mice that express the APP/PS1 transgene. Such mice show an AD-like disease, with memory loss and amyloid plaques that form in the brain.

Transplantation of ADSCs in these AD model mice decreased oxidative stress and promoted the growth of new neurons and glial cells in the subgranular and subventricular zones of the hippocampus, and, consequently improved the cognitive impairment in APP/PS1 transgenic AD mice.

These findings were published in Neural Regeneration Research (Vol. 9, No. 8, 2014), and provide theoretical and experimental evidence that ADSCs can be used to treat AD patients.