The Pathology Of Ad And Current Treatment
Alzheimers disease is a multifactorial brain disorder, with several pathogenic factors including genetic factors, oxidative stress, A-induced neurotoxicity, excitotoxicity, neuroinflammation, mitochondrial dysfunction, and cytoskeletal alteration of synapse components; therefore, it is complicated to determine its exact pathophysiologic cascade . There are several assumptions that explain AD neuropathy such as cholinergic assumption, oxidative stress assumption, and amyloid cascade assumption . However, approximately one-third of AD patients showed no radiographic signs of amyloid plaques . Therefore, more advanced diagnostic approaches should be developed to enable the early diagnosis of AD .
Amyloid cascade hypothesis assumed that the uncontrolled proteolytic processing of amyloid precursor protein results in the excessive accumulation of A deposits . APP is hydrolyzed through two major pathways; the non-amyloidogenic pathway that leads to the generation of non-pathogenic amyloid products and the amyloidogenic pathway that results in the formation of two forms of A peptides: predominant A-40 and fibrillogenic A-42 , involved in AD pathology . Accumulation of A plaques induces neurotoxicity and triggers a cascade of pathological events leading to neuroapoptosis in the central nervous system , .
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Stem Cell Alzheimers Disease Research
Could stem cell Alzheimers Disease research provide a potential path to future treatment or preventative measures?
The goal of todays post is to provide a review of the state of the field in this area including possible approaches and challenges.; You can watch a video covering the topic by Dr. Paul Knoepfler below on our stem cell YouTube channel. If you like this or our other videos please subscribe.
Alzheimers Disease Cord Blood And Stem Cells
There are currently 17 clinical trials investigating the application of stem cells in Alzheimers disease.
Studies using mice have shown some promise using stem cells to treat Alzheimers. One study found that the mice which had received human umbilical cord blood showed improved cognitive capacities, particularly learning, memory and motor function. The team conducting the study found that monocytes derived from human umbilical cord blood consumed and cleared the plaque fragments responsible for AD .
Scientists in Japan are treating the condition in trial stages by transplanting mesenchymal stem cells from patients fat tissue to the blood stream. Results so far offer hope that a cure could be found in the next few decades.
Human trials are currently underway to determine the safety and effectiveness of cord blood stem cells in Alzheimers. A combined phase 1/2a trial is expected to conclude in December 2015 .
Induced pluripotent stem cells are playing a crucial role in the study of Alzheimers disease. Taking skin cells from patients with Alzheimers scientists are able to reprogramme the cells to create neurons. These neurons show some of the key features of Alzheimers and could enable scientists to better understand how and why the brain produces the plaques and tangles that cause the disease. This in turn can lead to the development of effective therapies being developed .
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Cost Of Stem Cell Treatments
The cost of the initial treatment ranges from $5,000 to $10,000. The range in cost is dependent on the complexity of delivering the cells back to you. For example, spine conditions require multiple physicians to deliver the cells back to your body and this requires an increase in cost as multiple doctors are involved in the procedure. For many people the initial treatment procedure is all that is needed; however, for some conditions, subsequent treatments may be required and these are done at a reduced fee. Stem Cell Therapy procedures for Alzheimers patients are done at both our Dallas and Fort Worth practice locations.
Causes Of Alzheimer’s Disease
Alzheimer’s disease occurs when the brain cells die earlier than programmed, the cause of which is not fully understood. . Although it is seen very rare , it has genetic forms as well.
Although the exact cause of the disease is not known, a number of conditions causing risk include age, past depression, vascular diseases, and serious head injuries in the past.
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Stems Cells Used In Research
Stem cells have two important properties. First, they are able to reproduce themselves many times. Second, they can produce all the different cell types needed to make a human being, for instance heart cells, skin cells, nerve cells and so on. Stem cells can grow into brain cells, and as a result, have the potential to repair brain damage caused by neurological conditions, such as dementia. Although stem cells act in similar ways, there are types of stem cells in terms of where they come from: adult stem cells, which are present in the body throughout adult life; embryonic stem cells, which are only found in the embryo; and induced pluripotent stem cells , which can be created in the lab from ordinary adult cells and reverted back into a stem cell.
Alzheimers Society recognises that some donors and supporters have moral objections to the use of embryonic stem cells and therapeutic cloning. Currently, the Society aren’t funding any project;that uses embryonic stem cells. In the case that we did fund a research project of this kind, the wishes of any donor who does not want to support research that uses embryonic stem cells will be fully respected.
Stem Cell Research Centre
In 2014 we launched the Alzheimers Research UK Stem Cell Research Centre, a pioneering collaboration between researchers at the University of Cambridge and University College London which uses the latest human stem cell technology to understand the biology of Alzheimers disease and screen for new treatments.
Building on Nobel Prize-winning science, researchers at the Centre will use skin cells donated from people with rare genetic forms of Alzheimers and use cutting-edge stem cell techniques to transform them into working nerve cells in the laboratory. This involves re-setting the clock on skin cells turning them into stem cells which have the potential to form any cell type in the body. The researchers then use a cocktail of biological factors to encourage these stem cells to become working nerve cells. These cells have many of the features of the nerve cells in the brain that become damaged in dementia. You can read more about what stem cells are on our blog.
Prof Rick Livesey, who is leading the work of the Stem Cell Research Centre at the Gurdon Institute in Cambridge, has already shown that these nerve cells develop key features of Alzheimers in the dish and can be used to study the disease in more detail as well as to screen for new treatments.
The findings from this work are not only applicable to genetic forms of Alzheimers but could inform our understanding of the more common non-genetic forms too.
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Mechanistic Actions Of Transplanted Stem Cells For Treatment Of Ad
Regenerative medicine using stem cells could represent a promising therapeutic approach for the management of chronic disorders like AD; this is mainly attributed to the potential actions exerted by stem cells such as improving the neurogenic potential, exerting anti-inflammatory effect, presenting neurotrophic support, and having an anti-amyloidogenic potential .
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Researchers Test Stem Cells On Mice With Alzheimers Disease
In a mouse model of Alzheimers disease, amyloid beta clusters build up among neurons in a memory-related area of the brain.;Credit: Strittmatter Laboratory, Yale University Photo/Adam Kaufman
Researchers at the University of Michigan are testing the effectiveness of transplanted stem cells on mice with Alzheimers Disease . After implanting human neural stem cells into the brains of affected mice, they saw improvement in recognition, spatial memory and learning.1
The research team, led by Dr. Eva Feldman, reported its results in an article published in Nature earlier this year. UM scientists completed a proof-of-concept study using mice with genes that mimic AD. In the study, they transplanted human neural stem cells into the fimbria fornix. This region of the brain serves the hippocampus.
At 4 weeks and 16 weeks post-transplant, scientists observed significant changes in cognition for two hippocampus-centered tasks. Scientists believe the hippocampus controls emotion, memory and the autonomic nervous system. The team also noted that the test mice showed a marked decrease in their amyloid plaque load. Further, the researchers found that the transplanted stem cells did not trigger a significant immune system reaction. The results of the study suggest that stem cell transplantation could potentially provide therapeutic treatment for AD.
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What Is Unique About Receiving Stem Cell Therapy Through Trustem Cell Therapy For Alzheimers Disease
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Our focus is safety, efficacy, and patient-centric care when providing access to superior stem cell therapy.
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We utilize only board certified surgeons, physicians and accredited clinicians to provide care for patients.
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Laboratory protocols are developed and refined by our PhD Neuroscientist.
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A clinical team with expertise in practicing cellularbased medicine.
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Accredited Surgical Centers for enhanced procedural and patient safety
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Targeted administration methods that direct stem cells toward specificareas of injury which include the joints, brain, spine, lungs, etc
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Skilled Patient Advocates who are trained to provide truthful, realistic expectations resulting from stem cell therapy. We do not make outlandish promises of cures or inaccurate claims related to improvement rates.
Induced Pluripotent Stem Cells
iPSCs were first obtained from mouse fibroblasts in 2006. They are derived in vitro from mature somatic cells, usually adult dermal fibroblasts, by small-molecule therapy or viral vectormediated upregulation of transcription factors. Genetic modification makes them pluripotent and ESC-like in terms of phenotypic and differentiation capacity.
However, the following unresolved questions about the use of iPSCs pose huge obstacles to their clinical application: Teratoma formation, long-term safety and effectiveness, tumorigenicity, immunogenicity, patient genetic defects, optimal reprogramming and so forth.
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Alzheimer’s Society’s View On Stem Cell Research
Alzheimers Society supports the advancement of stem cell research to help understand the causes of dementia and to find new cures.
Stem cells can grow into brain cells, and as a result, may have the potential to repair brain damage caused by neurological conditions, such as dementia. Although stem cells act in similar ways, there are types of stem cells in terms of where they come from: adult stem cells, which are present in the body throughout adult life; embryonic stem cells, which are only found in the embryo; and induced pluripotent stem cells , which can be created in the lab from ordinary adult cells and reverted back into a stem cell.
Alzheimers Society recognises that some donors and supporters have ethical objections to the use of embryonic stem cells. Currently, the Society aren’t funding any project;that uses embryonic stem cells. In the case that we did fund a research project of this kind, the wishes of any donor who does not want to support research that uses embryonic stem cells will be fully respected.
What Causes Alzheimers Disease
The exact cause is unknown. Some individuals have a genetic tendency toward early Alzheimers Disease. These individuals can start seeing symptoms in their early 50s. There is also evidence linking brain injury earlier in life to Alzheimers Disease later on. Disease of the blood vessels of the brain with small or micro strokes also has an association. Many individuals with Alzheimers Disease appear to have multiple or mixed causes. The build of a protein called amyloid in the brain is strongly associated with Alzheimers Disease. Currently, the tests available for early detection of amyloid in the brain are too expensive for widespread use. More affordable tests are being developed.
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Can Stem Cell Research Help With Alzheimers
It has long been hoped that stem cell therapies could be used to repair the damage caused by diseases such as Alzheimers.
Although stem cell biology is a relatively new field, promising animal studies are beginning to show how stem cells might be able to treat diseases of the brain.
New research from Professor Eva Feldman at the University of Michigan has been testing this idea.
Her research group placed human neural stem cells into the brains of mice that were showing the symptoms of Alzheimers. The transplanted cells were put into the hippocampus, an area of the brain responsible for memory. The mice were then monitored to look for any changes in their thinking and memory skills.
Stem Cells Model Genetic Risk For Developing Alzheimers Disease
AD, the most frequent cause of dementia, affects an estimated 24 million people worldwide. With very limited treatment options, scientists are looking for ways to understand the disease better. One hallmark of AD is the emergence of so-called beta-amyloid plaques, clumps of beta-amyloid protein accumulating in the brain and thought to be toxic to adjacent neurons. The causes for Alzheimers disease and the formation of beta-amyloid plaques are still largely unknown but;genetic studies found that a gene called APOE, which is involved in cholesterol metabolism and transport, is linked to AD in the elderly. The APOE gene exists in different versions in people, APOE2, APOE3 and APOE4, but the APO4 gene comes with a relatively higher risk of developing AD.
Curiously, in the brain, its mostly the supporting cells called astrocytes rather than the neurons that make ApoE protein. To find out if the APOE4 gene in astrocytes relates to AD,;Jinsoo Seo;and colleagues with;the;Daegu Gyeongbuk Institute of Science and Technology , South;Korea,;used human-induced stem cells carrying different versions of the APOE gene to make neurons and astrocytes;in the lab, and to study their interaction. The researchers found that astrocytes carrying the AD-associated APOE4 gene released more cholesterol than astrocytes with APOE3.
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Alzheimers Disease: How Could Stem Cells Help
Alzheimers disease is the most common cause of dementia. It is a complex disease that affects nerve cells in many parts of the brain, making effective treatment very challenging. Can stem cell research help us tackle this challenge in the future?
What do we know?
Alzheimers disease is the leading cause of dementia. People affected by AD commonly experience memory loss, confusion and mood swings.
The cause of AD is still unknown, but several theories focus on two proteins, called amyloid beta and tau, which are found in deteriorating areas of an AD brain.
Clumps of amyloid beta proteins form plaques that may prevent neurons from sending signals properly.
Tau protein is important for normal cell function, but researchers think that when tau gets gnarled up into tau tangles it prevents neurons from getting nutrition.
There is currently no cure for AD.
What are researchers investigating?
No stem cell treatments are currently approved for AD. Positive effects have been seen with neural stem cell transplants given to mice with a disease similar to AD, but researchers are still studying what these stem cells are doing and how they might help repair the brain.
What are the challenges?
There are many different neurons throughout the brain that are destroyed by AD, making each case unique and very difficult to treat.
Plaques and tangles:;
Altering Neurogenesis To Restore Memory Function
From the two studies above, stem cells were shown to reduce or protect neurons from toxic aggregation of misfolded protein. However, both studies failed to investigate the effects of plaques or neurofibrillary tangles clearance on cognitive function. A year later, published a study showing that cognitive decline in a transgenic mice model of AD could actually be rescued by NSC therapy without altering the levels of A or tau protein. Interestingly, a previous imaging study showed similar findings which suggested that plaques and tangles could accumulate for many years before cognitive function starts declining . also demonstrated that cognitive improvement correlated positively with neurogenesis as they found an increase in brain-derived neurotrophic factor , which has role in synaptogenesis and neuronal networking . From this we could hypothesize that the cause of dementia in AD is due to the reduction in neurogenesis caused by the exhaustion of NSCs from long-term toxic damage by A plaques or tau neurofibrillary tangles. Post-mortem immunohistochemical studies in AD cases to investigate co-localization between NSCs and aggregated proteins could be helpful to identify the interaction between A, tau and NSCs.
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Stem Cell Treatment For Dementia Clears Major Hurdle
A new stem cell-based treatment for progressive dementia just took a big step closer to the clinic.
UCLA researchers have successfully grown restorative brain cells in large batches, at high quality, suitable for transplantation in patients.The therapy is designed to repair damage to the brain from white matter stroke, a type of “silent stroke” that can kick off years of cognitive deterioration in the form of a disease called “vascular dementia” and can even accelerate Alzheimer’s disease. The new paper is published in the journal Stem Cell Research.
When neurons die, as happens in a stroke, the brain generally can’t grow new ones to replace them. Previously, researchers have tried growing replacement neurons in the lab from stem cells, with some success.
However, this project, led by S. Thomas Carmichael, MD, Ph.D., chair of the Department of Neurology at the David Geffen School of Medicine at UCLA and interim director of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, takes a different approach.
Instead of neurons, the stem cells are directed to become cells called astrocytes, a kind of brain cell that supports and influences neurons.
Silent strokes can lead to later dementia
Acute strokes in large blood vessels cause the symptoms most commonly associated with stroke, such as drooping face or weakness in one arm. But white matter strokes occur in tiny blood vessels, causing small damage that gradually accumulates over time.