Posts tagged alzheimer's disease
Articles and news from the latest research reports.
Scientists develop 3-D stem cell culture technique to better understand Alzheimer’s disease
A team of researchers at The New York Stem Cell Foundation Research Institute led by Scott Noggle, PhD, Director of the NYSCF Laboratory and the NYSCF – Charles Evans Senior Research Fellow for Alzheimer’s Disease, and Michael W. Nestor, PhD, a NYSCF Postdoctoral Research Fellow, has developed a technique to produce three-dimensional cultures of induced pluripotent stem (iPS) cells called embryoid bodies, amenable to live cell imaging and to electrical activity measurement. As reported in their Stem Cell Research study, these cell aggregates enable scientists to both model and to study diseases such as Alzheimer’s and Parkinson’s disease.
The NYSCF Alzheimer’s disease research team aims to better understand and to find treatments to this disease through stem cell research. For such disorders in which neurons misfire or degenerate, the NYSCF team creates “disease in a dish” models by reprogramming patients’ skin and or blood samples into induced pluripotent stem (iPS) cells that can become neurons and the other brain cells affected in the diseases.
The cells in our body form three-dimensional networks, essential to tissue function and overall health; however, previous techniques to form complex brain tissue resulted in structures that, while similar in form to naturally occurring neurons, undermined imaging or electrical recording attempts.
In the current study, the Noggle and Nestor with NYSCF scientists specially adapted two-dimensional culture methods to grow three-dimensional neuron structures from iPS cells. The resultant neurons were “thinned-out,” enabling calcium-imaging studies, which measure the electrical activity of cells like neurons.
"Combining the advantages of iPS cells grown in a 3D environment with those of a 2D system, our technique produces cells that can be used to observe electrical activity of putative networks of biologically active neurons, while simultaneously imaging them," said Nestor. "This is key to modeling and studying neurodegenerative diseases."
Neural networks, thought to underlie learning and memory, become disrupted in Alzheimer’s disease. By generating aggregates from iPS cells and comparing these to an actual patient’s brain tissue, scientists may uncover how disease interferes with these cell-to-cell interactions and understand how to intervene to slow or stop Alzheimer’s disease.
"This critical new tool developed by our Alzheimer’s team will accelerate Alzheimer’s research, enabling more accurate manipulation of cells to find a cure to this disease," said Susan L. Solomon, CEO of NYSCF.
(Source: eurekalert.org)
Surgical menopause may prime brain for stroke, Alzheimer’s
Women who abruptly and prematurely lose estrogen from surgical menopause have a two-fold increase in cognitive decline and dementia.
"This is what the clinical studies indicate and our animal studies looking at the underlying mechanisms back this up," said Brann, corresponding author of the study in the journal Brain. “We wanted to find out why that is occurring. We suspect it’s due to the premature loss of estrogen.”
In an effort to mimic what occurs in women, Brann and his colleagues looked at rats 10 weeks after removal of their estrogen-producing ovaries that were either immediately started on low-dose estrogen therapy, started therapy 10 weeks later or never given estrogen.
When the researchers caused a stroke-like event in the brain’s hippocampus, a center of learning and memory, they found the rodents treated late or not at all experienced more brain damage, specifically to a region of the hippocampus called CA3 that is normally stroke-resistant.
To make matters worse, untreated or late-treated rats also began an abnormal, robust production of Alzheimer’s disease-related proteins in the CA3 region, even becoming hypersensitive to one of the most toxic of the beta amyloid proteins that are a hallmark of Alzheimer’s.
Both problems appear associated with the increased production of free radicals in the brain. In fact, when the researchers blocked the excessive production, heightened stroke sensitivity and brain cell death in the CA3 region were reduced.
Interestingly the brain’s increased sensitivity to stressors such as inadequate oxygen was gender specific, Brann said. Removing testes in male rats, didn’t affect stroke size or damage.
Although exactly how it works is unknown, estrogen appears to help protect younger females from problems such as stroke and heart attack. Their risks of the maladies increase after menopause to about the same as males. Follow up studies are needed to see if estrogen therapy also reduces sensitivity to the beta amyloid protein in the CA3 region, as they expect, Brann noted.
Brann earlier showed that prolonged estrogen deprivation in aging rats dramatically reduces the number of brain receptors for the hormone as well as its ability to prevent strokes. Damage was forestalled if estrogen replacement was started shortly after hormone levels drop, according to the 2011 study in the journal Proceedings of the National Academy of Sciences.
The surprising results of the much-publicized Women’s Health Initiative – a 12-year study of 161,808 women ages 50-79 – found hormone therapy generally increased rather than decreased stroke risk as well as other health problems. Critics said one problem with the study was that many of the women, like Brann’s aged rats, had gone years without hormone replacement, bolstering the case that timing is everything.
(Source: eurekalert.org)
Hypertension Could Bring Increased Risk for Alzheimer’s disease
A study in the Journal of the American Medical Association Neurology suggests that controlling or preventing risk factors, such as hypertension, earlier in life may limit or delay the brain changes associated with Alzheimer’s disease and other age-related neurological deterioration.
Dr. Karen Rodrigue, assistant professor in the UT Dallas Center for Vital Longevity (CVL), was lead author of a study that looked at whether people with both hypertension and a common gene had more buildup of a brain plaque called amyloid protein, which is associated with Alzheimer’s disease. Scientists believe amyloid is the first symptom of Alzheimer’s disease and shows up a decade or more before symptoms of memory impairment and other cognitive difficulties begin. The gene, known as APOE 4, is carried by 20 percent of the population.
Until recently, amyloid plaque could be seen only at autopsy, but new brain scanning techniques allow scientists to see plaque in living brains of healthy adults. Findings from both autopsy and amyloid brain scans show that at least 20 percent of typical older adults carry elevated levels of amyloid, a substance made up mostly of protein that is deposited in organs and tissues.
“I became interested in whether hypertension was related to increased risk of amyloid plaques in the brains of otherwise healthy people,” Rodrigue said. “Identifying the most significant risk factors for amyloid deposition in seemingly healthy adults will be critical in advancing medical efforts aimed at prevention and early detection.”
Based on evidence that hypertension was associated with Alzheimer’s disease, Rodrigue suspected that the combination of hypertension and the presence of the APOE-e4 gene might lead to particularly high levels of amyloid plaque in healthy adults.
New target for Alzheimer’s disease treatment
Researchers have found new evidence that insulating cells, the cells that protect our nerves, can be made and added to the central nervous system throughout our lifetime.
Chief investigator on the paper, Menzies Research Institute Tasmania’s Dr Kaylene Young, says there is now evidence that these cells may not be the passive by-standers to brain function that we once thought.
“Previously it was thought that most insulating cells in an adult brain were born before reaching adulthood,” Dr Young said.
“This research shows that new insulating cells are made from an immature cell type found in our brains, called oligodendrocyte precursor cells (OPCs).
“In fact, new insulation is added to brain circuits every day, which changes the way the circuits function.
“This process is likely to be very important for learning, memory, vision and co-ordination.”
“This finding may have important implications for sufferers of Alzheimer’s Disease, multiple sclerosis and other neurological disorders.
Alzheimer’s disease is the most common form of dementia. There are over 321,600 Australians living with dementia and without a medical breakthrough, the number of people with dementia is expected to be almost 900,000 by 2050. (Alzheimer’s Australia)
In Alzheimer’s Disease (AD) many nerve cells die. This causes patients with AD to progressively lose their ability to think clearly and remember things, and they can also experience problems with movement and co-ordination.
A single insulating cell in the brain supports the health and function of many nerve cells.
We know from diseases like multiple sclerosis that losing insulation makes nerve cells extremely vulnerable to damage and death.
This may also be true for AD, and there is an increasing amount of evidence that supports the idea that insulating cells are damaged before nerve cells and could contribute directly to nerve cell loss.
By studying brain scans from patients with AD, researchers previously found that the amount of insulation that is damaged matched the level of the patient’s dementia. The more damaged the insulation, the worse the person’s memory problems.
Dr Young’s research team are now investigating ways to hijack the natural ability of OPCs to make new insulating cells, and repair the insulation damage that is seen in the brains of AD patients.
“Stimulating OPCs in the brain is an appealing possibility since they are found throughout all brain regions, meaning that they are already where they need to be to make new insulating cells!
“We expect that increasing brain insulation, to re-wrap the nerve cells, will prevent more nerve cells from dying. Protecting nerve cells would prevent the rapid mental deterioration seen in people after they are diagnosed with AD,” Dr Young said.
This work was published this month, in the international journal, Neuron and involved collaboration with researchers in the United Kingdom and Japan.
(Source: utas.edu.au)
Dynamic new software improves care of aging brain
Innovative medical records software developed by geriatricians and informaticians from the Regenstrief Institute and the Indiana University Center for Aging Research will provide more personalized health care for older adult patients, a population at significant risk for mental health decline and disorders.
A new study published in eGEMs, a peer-reviewed online publication recently launched by the Electronic Data Methods Forum, unveils the enhanced Electronic Medical Record Aging Brain Care Software, an automated decision-support system that enables care coordinators to track the health of the aging brain and help meet the complex biopsychosocial needs of patients and their informal caregivers.
The eMR-ABC captures and monitors the cognitive, functional, behavioral and psychological symptoms of older adults suffering from dementia or depression. It also collects information on the burden placed on patients’ family caregivers.
Utilizing this information, the software application provides decision support to care coordinators, who, working with physicians, social workers and other members of the health care team, create a personalized care plan that includes evidence-based non-pharmacological protocols, self-management handouts and alerts of medications with potentially adverse cognitive effects. The software’s built-in engine tracks patient visits and can be used to generate population reports for specified indicators such as cognitive decline or caregiver burnout.
"The number of older adults is growing rapidly. Delivering personalized care to this population is difficult and requires the ability to track a large number of mental and physical indicators," said Regenstrief Institute investigator Malaz Boustani, M.D., MPH, associate director of the IU Center for Aging Research and associate professor of medicine at the IU School of Medicine. He is senior author of the new study. "The software we have developed will help care coordinators measure the many needs of patients and their loved ones and monitor the effectiveness of individualized care plans."
In clinical trials over the past decade, Regenstrief and the IU Center for Aging Research investigator-clinicians developed and demonstrated the efficacy of an Alzheimer’s disease collaborative care model called the Aging Brain Care Medical Home. A hallmark of the ABC-MedHome is the employment of care coordinators who help clinicians identify and manage processes and protocols for Alzheimer’s patients who receive care in local primary care physician offices. The ABC-MedHome has been shown to improve the quality of Alzheimer’s care and decrease its burden on the health care system.
Within the ABC-MedHome program, Dr. Boustani and colleagues have now developed, tested, implemented and improved software that is sensitive to the clinical needs of a multispecialty team of professionals who provide care to complex patients across a variety of settings. The new software allows tracking of individual patient health outcomes as well as the ability to follow the status of an entire patient population with key quality, health and cost metrics.
"Integration of the eMR-ABC program within Wishard-Eskenazi Health was pivotal to our receipt in 2012 of a Health Care Innovation Challenge award from the Centers for Medicare & Medicaid Services to expand from care of 250 patients to 2,000 patients plus caregivers," said Dr. Boustani, who is medical director of the Wishard Healthy Aging Brain Center and also an IU Health geriatrician. "New models of care, supported by population health management tools, are needed if we are to provide improved quality of care and encourage better health outcomes for our patients and be cost sensitive. We are using health information technology to manage high-risk populations while achieving the triple aim of better health and better care at lower cost."
(Source: eurekalert.org)
Sleep loss precedes Alzheimer’s symptoms
Sleep is disrupted in people who likely have early Alzheimer’s disease but do not yet have the memory loss or other cognitive problems characteristic of full-blown disease, researchers at Washington University School of Medicine in St. Louis report March 11 in JAMA Neurology.
The finding confirms earlier observations by some of the same researchers. Those studies showed a link in mice between sleep loss and brain plaques, a hallmark of Alzheimer’s disease. Early evidence tentatively suggests the connection may work in both directions: Alzheimer’s plaques disrupt sleep, and lack of sleep promotes Alzheimer’s plaques.
“This link may provide us with an easily detectable sign of Alzheimer’s pathology,” says senior author David M. Holtzman, MD, the Andrew B. and Gretchen P. Jones Professor and head of Washington University’s Department of Neurology. “As we start to treat people who have markers of early Alzheimer’s, changes in sleep in response to treatments may serve as an indicator of whether the new treatments are succeeding.”
Sleep problems are common in people who have symptomatic Alzheimer’s disease, but scientists recently have begun to suspect that they also may be an indicator of early disease. The new paper is among the first to connect early Alzheimer’s disease and sleep disruption in humans.
(Image: iStockphoto)
Sleep Discovery Could Lead to Therapies That Improve Memory
A team of sleep researchers led by UC Riverside psychologist Sara C. Mednick has confirmed the mechanism that enables the brain to consolidate memory and found that a commonly prescribed sleep aid enhances the process. Those discoveries could lead to new sleep therapies that will improve memory for aging adults and those with dementia, Alzheimer’s and schizophrenia.
The groundbreaking research appears in a paper, “The Critical Role of Sleep Spindles in Hippocampal-Dependent Memory: A Pharmacology Study,” published in the Journal of Neuroscience.
Earlier research found a correlation between sleep spindles — bursts of brain activity that last for a second or less during a specific stage of sleep — and consolidation of memories that depend on the hippocampus. The hippocampus, part of the cerebral cortex, is important in the consolidation of information from short-term to long-term memory, and spatial navigation. The hippocampus is one of the first regions of the brain damaged by Alzheimer’s disease.
Mednick and her research team demonstrated, for the first time, the critical role that sleep spindles play in consolidating memory in the hippocampus, and they showed that pharmaceuticals could significantly improve that process, far more than sleep alone.
In addition to Mednick the research team includes: Elizabeth A. McDevitt, UC San Diego; James K. Walsh, VA San Diego Healthcare System, La Jolla, Calif; Erin Wamsley, St. Luke’s Hospital, St. Louis, Mo.; Martin Paulus, Stanford University; Jennifer C. Kanady, Harvard Medical School; and Sean P.A. Drummond, UC Berkeley.
“We found that a very common sleep drug can be used to increase verbal memory,” said Mednick, the lead author of the paper that outlines results of two studies conducted over five years with a $651,999 research grant from the National Institutes of Health. “This is the first study to show you can manipulate sleep to improve memory. It suggests sleep drugs could be a powerful tool to tailor sleep to particular memory disorders.”
Drug Shows Potential to Delay Onset or Progression of Alzheimer’s Disease
A research team led by Robert Nagele, PhD, of the New Jersey Institute for Successful Aging (NJISA) at the University of Medicine and Dentistry of New Jersey (UMDNJ)-School of Osteopathic Medicine, has demonstrated that the anti-atherosclerosis drug darapladib can significantly reduce leaks in the blood brain barrier. This finding potentially opens the door to new therapies to prevent the onset or the progression of Alzheimer’s disease. Writing in the Journal of Alzheimer’s Disease (currently in press), the researchers describe findings involving the use of darapladib in animal models that had been induced to develop diabetes mellitus and hypercholesterolemia (DMHC), which are considered to be major risk factors for Alzheimer’s disease.
“Diabetes and hypercholesterolemia are associated with an increased permeability of the blood-brain barrier, and it is becoming increasingly clear that this blood-brain barrier breakdown contributes to neurodegenerative diseases such as Alzheimer’s,” Nagele said. “Darapladib appears to be able to reduce this permeability to levels comparable to those found in normal, non-DMHC controls, and suggests a link between this permeability and the deposition of amyloid peptides in the brain.”
The study involved 28 animal (pig) models that were divided into three groups – DMHC animals treated with a 10 mg/day dose of darapladib; DMHC animals that received no treatment; and non-DMHC controls. Post-mortem analysis of the brains of the darapladib-treated animals showed significant decreases in blood-brain barrier leakage and in the density of amyloid-positive neurons in the cerebral cortices. Interestingly, the amyloid peptides that leaked into the brain tissue were found almost exclusively in the pyramidal neurons of the cerebral cortex, one of the earliest pathologies of the development of Alzheimer’s disease.
“Because our results suggest that these metabolic disorders can trigger neurodegenerative changes through blood-brain barrier compromise, therapies – such as darapladib – that can reduce vascular leaks have great potential for delaying the onset or slowing the progression of diseases like Alzheimer’s,” said the study’s lead author, Nimish Acharya, PhD, of the NJISA and the UMDNJ-Graduate School of Biomedical Sciences. “The clinical, caregiving and financial impact of such an effect cannot be overestimated.”
(Source: newswise.com)
Scientists Identify Buphenyl as a Possible Drug for Alzheimer’s disease
Buphenyl, an FDA-approved medication for hyperammonemia, may protect memory and prevent the progression of Alzheimer’s disease. Hyperammonemia is a life-threatening condition that can affect patients at any age. It is caused by abnormal, high levels of ammonia in the blood.
Studies in mice with Alzheimer’s disease (AD) have shown that sodium phenylbutyrate, known as Buphenyl, successfully increases factors for neuronal growth and protects learning and memory, according to neurological researchers at the Rush University Medical Center.
Results from the National Institutes of Health funded study, recently were published in the Journal of Biological Chemistry.
“Understanding how the disease works is important to developing effective drugs that protect the brain and stop the progression of Alzheimer’s disease,” said Kalipada Pahan, PhD, the Floyd A. Davis professor of neurology at Rush and lead investigator of this study.
A family of proteins known as neurotrophic factors help in survival and function of neurons. Past research indicates that these proteins are drastically decreased in the brain of patients with Alzheimer’s disease (AD).
“Neurotrophic factor proteins could be increased in the brain by direct injection or gene delivery,” said Pahan. “However, using an oral medication to increase the level of these protein may be the best clinical option and a cost effective way to increase the level of these proteins directly in the brain.”
“Our study found that after oral feeding, Buphenyl enters into the brain, increases these beneficial proteins in the brain, protects neurons, and improves memory and learning in mice with AD-like pathology,” said Pahan.
In the brain of a patient with AD, two abnormal structures called plaques and tangles are prime suspects in damaging and killing nerve cells. While neurons die, other brain cells like astroglia do not die.
The study findings indicate that Buphenyl increases neurotrophic factors from astroglia. Buphenyl stimulates memory-related protein CREB (cyclic AMP response element-binding protein) using another protein known as Protein Kinase C (PKC) and increases neurotrophic factors in the brain.
"Now we need to translate this finding to the clinic and test Buphenyl in Alzheimer’s disease patients,” said Pahan. “If these results are replicated in Alzheimer’s disease patients, it would open up a promising avenue of treatment of this devastating neurodegenerative disease.”
Drugs targeting blood vessels may be candidates for treating Alzheimer’s
University of British Columbia researchers have successfully normalized the production of blood vessels in the brain of mice with Alzheimer’s disease (AD) by immunizing them with amyloid beta, a protein widely associated with the disease.
While AD is typically characterized by a build-up of plaques in the brain, recent research by the UBC team showed a near doubling of blood vessels in the brain of mice and humans with AD.
The new study, published online last week in Scientific Reports, a Nature journal, shows a reduction of brain capillaries in mice immunized with amyloid beta – a phenomenon subsequently corroborated by human clinical data – as well as a reduction of plaque build-up.
“The discovery provides further evidence of the role that an overabundance of brain blood vessels plays in AD, as well as the potential efficacy of amyloid beta as basis for an AD vaccine,” says lead investigator Wilfred Jefferies, a professor in UBC’s Michael Smith Laboratories.
“Now that we know blood vessel growth is a factor in AD, if follows that drugs targeting blood vessels may be good candidates as an AD treatment.”
AD accounts for two-thirds of all cases of dementia. The number of Canadians living with dementia is expected to reach 1.4 million by 2013, according to the Alzheimer’s Society of Canada.