Posts tagged alzheimer's disease
Articles and news from the latest research reports.
When trying to determine the root cause of a person’s dementia, using an MRI can effectively and non-invasively screen patients for Alzheimer’s disease or Frontotemporal Lobar Degeneration (FTLD), according to a new study by researchers from the Perelman School of Medicine at the University of Pennsylvania. Using an MRI-based algorithm effectively differentiated cases 75 percent of the time, according to the study, published in the December 26th, 2012, issue of Neurology, the medical journal of the American Academy of Neurology. The non-invasive approach reported in this study can track disease progression over time more easily and cost-effectively than other tests, particularly in clinical trials testing new therapies.
Researchers used the MRIs to predict the ratio of two biomarkers for the diseases - the proteins total tau and beta-amyloid - in the cerebrospinal fluid. Cerebrospinal fluid analyses remain the most accurate method for predicting the disease cause, but requires a more invasive lumbar puncture. “Using this novel method, we obtain a single biologically meaningful value from analyzing MRI data in this manner and then we can derive a probabilistic estimate of the likelihood of Alzheimer’s or FTLD,” said the study’s lead author, Corey McMillan, PhD, of the Perelman School of Medicine and Frontotemporal Degeneration Center at the University of Pennsylvania.
Using the MRI prediction method was 75 percent accurate at identifying the correct diagnosis in both patients with pre-confirmed disease diagnoses and those with biomarker levels confirmed by lumbar punctures, which shows comparable overlap between accuracy of the MRI and lumbar puncture methods. “For those remaining 25 percent of cases that are borderline, a lumbar puncture testing spinal fluid may provide a more accurate estimate of the pathological diagnosis.”
Accurate tests to measure disease progression are very important in neurodegenerative diseases, especially as clinical trials test new therapies to slow or stop the progression or the disease. Biomarkers for neurodegenerative diseases have been steadily improving, with new developments including spinal fluid tests detecting tau and amyloid-beta protein levels and other neuroimaging techniques developed at Penn Medicine, as part of the Alzheimer’s Disease Neuroimaging Initiative. While a spinal fluid test can be used to accurately pinpoint whether disease-specific proteins are present, the test requires a more invasive lumbar puncture making it more difficult to repeat over time. And for studies using other imaging techniques, such as test measuring whole brain volume, reduced sensitivity of the measurement requires more patients to be enrolled in clinical trials for statistical power to be achieved.
“Since this method yields a single biological value, it is possible to use MRI to screen patients for inclusion in clinical trials in a cost-effective manner and to provide an outcome measure that optimizes power in drug treatment trials,” the authors concluded.
PredictAD software promises early diagnosis of Alzheimer’s
Scientists at VTT Technical Research Centre in Finland have developed new software called PredictAD that could significantly boost the early diagnosis of Alzheimer’s disease.
The comparative software contrasts patient’s measurements with those of other patients kept in large databases, then visualizes the status of the patient with an index and graphics.
The support system and imaging methods were developed by VTT and Imperial College London.
The researchers used material compiled in the U.S. by the Alzheimer’s Disease Neuroimaging Initiative based on the records of 288 patients with memory problems. Nearly half of them, or 140 individuals, were diagnosed with Alzheimer’s disease on average 21 months after the initial measurements, which is about the same as the current European average of 20 months.
The researchers concluded that half of the patients could have been diagnosed with the disease around a year earlier, or nine months after the initial measurements. They say the accuracy of the predictions was comparable to clinical diagnosis.
There are several advantages of an early diagnosis of Alzheimer’s. It can delay institutionalization and slow down the progress of the disease. It is also advantageous from the clinical trials perspective because if patients caught early can be included in the trials, treatment is likely to be more effective.
Working towards the same goal, researchers at Lancaster University in the U.K. recently developed an eye test method to detect early signs of Alzheimer’s.
The VTT researchers will spend the next five years carrying out the test at memory clinics in Europe. They also hope to expand its scope to include other illnesses that cause dementia. According to 2010 figures, an estimated 35.6 people live with dementia worldwide, and that number is expected to rise to 65.7 million by 2030.
The findings of the research were published in the Journal of Alzheimer’s Disease in November 2012. VTT cooperated with the University of Eastern Finland and Copenhagen University Hospital Rigshospitalet on this project.
Even the Smallest Possible Stroke Can Damage Brain Tissue and Impair Cognitive Function
Blocking a single tiny blood vessel in the brain can harm neural tissue and even alter behavior, a new study from the University of California, San Diego has shown. But these consequences can be mitigated by a drug already in use, suggesting treatment that could slow the progress of dementia associated with cumulative damage to miniscule blood vessels that feed brain cells. The team reports their results in the December 16 advance online edition of Nature Neuroscience.
"The brain is incredibly dense with vasculature. It was surprising that blocking one small vessel could have a discernable impact on the behavior of a rat," said Andy Y. Shih, lead author of the paper who completed this work as a postdoctoral fellow in physics at UC San Diego. Shih is now an assistant professor at the Medical University of South Carolina.
Working with rats, Shih and colleagues used laser light to clot blood at precise points within small blood vessels that dive from the surface of the brain to penetrate neural tissue. When they looked at the brains up to a week later, they saw tiny holes reminiscent of the widespread damage often seen when the brains of patients with dementia are examined as a part of an autopsy.
These micro-lesions are too small to be detected with conventional MRI scans, which have a resolution of about a millimeter. Nearly two dozen of these small vessels enter the brain from a square millimeter area of the surface of the brain.
"It’s controversial whether that sort of damage has consequences, although the tide of evidence has been growing as human diagnostics improve," said David Kleinfeld, professor of physics and neurobiology, who leads the research group.
To see whether such minute damage could change behavior, the scientists trained thirsty rats to leap from one platform to another in the dark to get water.
The rats readily jump if they can reach the second platform with a paw or their snout, or stretch farther to touch it with their whiskers. Many rats can be trained to rely on a single whisker if the others are clipped, but if they can’t feel the far platform, they won’t budge.
"The whiskers line up in rows and each one is linked to a specific spot in the brain," Shih said. "By training them to use just one whisker, we were able to distill a behavior down to a very small part of the brain."
When Shih blocked single microvessels feeding a column of brain cells that respond to signals from the remaining whisker, the rats still crossed to the far platform when the gap was small. But when it widened beyond the reach of their snouts, they quit.
The FDA-approved drug memantine, prescribed to slow one aspect of memory decline associated with Alzheimer’s disease, ameliorated these effects. Rats that received the drug jumped whisker-wide gaps, and their brains showed fewer signs of damage.
"This data shows us, for the first time, that even a tiny stroke can lead to disability," said Patrick D. Lyden, a co-author of the study and chair of the department of neurology at Cedars-Sinai Medical Center in Los Angeles. "I am afraid that tiny strokes in our patients contribute—over the long term—to illness such as dementia and Alzheimer’s disease," he said, adding that "better tools will be required to tell whether human patients suffer memory effects from the smallest strokes."
“We used powerful tools from biological physics, many developed in Kleinfeld’s laboratory at UC San Diego, to link stroke to dementia on the unprecedented small scale of single vessels and cells,” Shih said. “At my new position at MUSC, I plan to work on ways to improve the detection of micro-lesions in human patients with MRI. This way clinicians may be able to diagnose and treat dementia earlier.”
Better understanding of the cause of Alzheimer’s disease
Alzheimer’s disease is the most common form of dementia, affecting over 35 million people worldwide. It is generally assumed that the clumping of beta-amyloid (Aß) protein causes neuronal loss in patients. Medication focuses on reducing Aß42, one of the most common proteins and the most harmful. University of Twente PhD student Annelies Vandersteen is refining the current approach. She explains: “The results of my research provide a broader understanding of the processes that lead to Alzheimer’s disease and in this way may help to bring about new medication”.
The Aß protein occurs in the body in various lengths, ranging from 33 to 49 amino acids. The shorter varieties are regarded as ‘safe’, unlike the longer ones – Aß42 and longer – which are highly aggregating. Current therapeutic strategy tries to reduce the clumping of Aß42, and its harmful effects, by limiting the release of Aß42. Reducing Aß42 production at the same time results in a rise in Aß38 levels. Vandersteen comments: “One of the findings of my research is that small amounts of Aß38 can in fact increase or temper the clumping and toxic effects of longer Aß proteins. The processes that result in Alzheimer’s disease are determined by the whole spectrum of Aß proteins. So the picture is far less black and white than has been assumed so far, and less common forms of Aß are far less harmless than we thought.”
The study
Vandersteen examined the protein mixtures in a laboratory situation. She devised a series of experiments based on a computer-calculated hypothesis. The behaviour of the various Aß proteins and mixtures was studied in detail and described using various biophysical techniques. The influence of the various Aß proteins and mixtures on neurons was then studied in a cell culture.
(Source: alphagalileo.org)
Kentucky team inhibits Alzheimer’s biomarkers in animal model by targeting astrocytes
A research team composed of University of Kentucky researchers has published a paper which provides the first direct evidence that activated astrocytes could play a harmful role in Alzheimer’s disease. The UK Sanders-Brown Center on Aging has also received significant new National Institutes of Health (NIH) funding to further this line of study.
Chris Norris, an associate professor in the UK College of Medicine Department of Molecular and Biomedical Pharmacology, as well as a member of the faculty at the UK Sanders-Brown Center on Aging, is the senior author on a paper published recently in the Journal of Neuroscience, entitled “Targeting astrocytes to ameliorate neurologic changes in a mouse model of Alzheimer’s disease.” The first author on the article, Jennifer L. Furman, was a graduate student in the Norris laboratory during completion of the study.
The astrocyte is a very abundant non-neuronal cell type that performs absolutely critical functions for maintaining healthy nervous tissue. However, in neurodegenerative diseases, like Alzheimer’s disease, many astrocytes exhibit clear physical changes often referred to as “astrocyte activation.” The appearance of activated astrocytes at very early stages of Alzheimer’s has led to the idea that astrocytes contribute to the emergence and/or maintenance of other pathological markers of the disease, including synaptic dysfunction, neuroinflammation and accumulation of amyloid plaques.
Using an animal model, researchers directly modulated the activation state of hippocampal astrocytes using a form of gene therapy.
Mice received the gene therapy at a very young age, before the development of extensive amyloid plaque pathology, and were assessed 10 months later on a variety of Alzheimer’s biomarkers.
The research team found that inhibition of astrocyte activation blunted the activation of microglia (a cell that mediates neuroinflammation), reduced toxic amyloid levels, improved synaptic function and plasticity, and preserved cognitive function.
Norris and collaborators suggest that similar astrocyte-based approaches could be developed to treat humans suffering from Alzheimer’s disease, or possibly other neurodegenerative diseases. This study provides proof of principle that therapeutically targeting astrocytes can be beneficial.
(Source: eurekalert.org)
UAlberta medical researchers make key discovery in fight against Alzheimer’s disease
Medical researchers at the University of Alberta have discovered a drug intended for diabetes appears to restore memory in Alzheimer’s brain cells.
Jack Jhamandas, a researcher with the Faculty of Medicine & Dentistry at the U of A, is the principal investigator with the team whose research results were recently published in the peer-reviewed publication The Journal of Neuroscience. He works in the Division of Neurology.
The team took brain tissue from animal models with Alzheimer’s disease and tested the tissue in the lab, looking specifically at the cells’ memory capacity. When brain cells are shocked by a barrage of electrical impulses, the cells “remember” the experience and this is a typical way to test or measure memory in the lab setting.
Amyloid protein, which is found in abnormally large amounts in the memory and cognition parts of the brains of Alzheimer’s patients, diminishes memory. A sister protein, known as amylin, which comes from the pancreas of diabetic patients, has the same impact on memory cells.Jhamandas and his team demonstrated last year that a diabetes drug that never made it to market, known as AC253, could block the toxic effects of amyloid protein that lead to brain cell death.
In the lab, Jhamandas and his teammates, which included Ryoichi Kimura, a visiting scientist from Japan, tested the memory of normal brain cells and those with Alzheimer’s—both from animal models. When the drug AC253 was given to brain cells with Alzheimer’s and the shock memory tests were redone, memory was restored to levels similar to those in normal cells.
“This is very important because it tells us that drugs like this might be able to restore memory, even after Alzheimer’s disease may have set in,” says Jhamandas.
Combination of imaging exams improves Alzheimer’s diagnosis
A combination of diagnostic tests, including imaging and cerebrospinal fluid biomarkers can improve prediction of conversion from mild cognitive impairment (MCI) to Alzheimer’s disease, according to a new study published online in the journal Radiology.
"Because new treatments are likely to be most effective at the earliest stages of Alzheimer’s disease, there is great urgency to develop sensitive markers that facilitate detection and monitoring of early brain changes in individuals at risk," said Jeffrey R. Petrella, M.D., associate professor of radiology, division of neuroradiology, and director of the Alzheimer’s Disease Research Lab at Duke University Medical Center (DUMC) in Durham, N.C. "Our study looks at whether more sophisticated diagnostic tests such as magnetic resonance imaging (MRI), positron emission tomography (PET) and spinal fluid protein analysis might provide additional prognostic information, compared to more readily available cognitive and blood testing."
According to the World Health Organization, more than 35 million people worldwide are living with Alzheimer’s disease, which is incurable, and the prevalence is expected to double by 2030.
"Although there is no cure for Alzheimer’s disease, there are four symptomatic treatments that might provide some benefits," said coauthor P. Murali Doraiswamy, M.D., professor of psychiatry at DUMC. "So developing the right combination of diagnostic tests is critical to make sure we enable an accurate and early diagnosis in patients, so they can evaluate their care options."
Alzheimer’s researcher reveals a protein’s dual destructiveness – and therapeutic potential
A scientist at the University of British Columbia and Vancouver Coastal Health has identified the molecule that controls a scissor-like protein responsible for the production of plaques – the telltale sign of Alzheimer’s disease (AD).
The molecule, known as GSK3-beta, activates a gene that creates a protein, called BACE1. When BACE1 cuts another protein, called APP, the resulting fragment – known as amyloid beta – forms tiny fibers that clump together into plaques in the brain, eventually killing neural cells.
Using an animal model, Dr. Weihong Song, Canada Research Chair in Alzheimer’s Disease and professor of psychiatry, found that disabling GSK3-beta’s effect in mice resulted in less BACE1 and far fewer deposits of amyloid in their brains. Song’s research, published online in the Journal of Clinical Investigation, also found that such mice performed better than untreated mice on memory tests.
Previous research had shown that GSK3-beta spurred the growth of twisted fibers inside neurons, known as tangles – another hallmark of AD. Song says his discovery of the protein’s dual destructiveness makes it a promising target for drug research.
GSK3-beta, however, is a versatile enzyme that controls many vital physiological functions. The drug used to inhibit GSK3-beta in the mice is too indiscriminate, and could cause several serious side effects, including cancer.
“If we can find a way to stop GSK3-beta’s specific reaction with BACE1, and still leave it intact to perform other crucial tasks, we have a much better chance of treating AD and preventing its progression,” says Song, a member of the Brain Research Centre at UBC and the Vancouver Coastal Health Research Institute (VCHRI), and Director of the Townsend Family Laboratories at UBC.
(Source: publicaffairs.ubc.ca)
University of Minnesota researchers find new target for Alzheimer’s drug development
Researchers at the University of Minnesota’s Center for Drug Design have developed a synthetic compound that, in a mouse model, successfully prevents the neurodegeneration associated with Alzheimer’s disease.
In the pre-clinical study, researchers Robert Vince, Ph.D.; Swati More, Ph.D.; and Ashish Vartak, Ph.D., of the University’s Center for Drug Design, found evidence that a lab-made compound known as psi-GSH enables the brain to use its own protective enzyme system, called glyoxalase, against the Alzheimer’s disease process.
The discovery is published online in the American Chemical Society journal ACS Chemical Neuroscience and presents a new target for the design of anti-Alzheimer’s and related drugs.
“While most other drugs under development and on the market attempt to slow down or reverse the Alzheimer’s processes, our approach strikes at a root cause by enabling the brain itself to fight the disease at a very early stage,” said Vince, the study’s lead researcher and director of the Center for Drug Design. “As is the case with all drug development, these studies need to be replicated in human patients before coming to any firm conclusions.”
Scientists Discover Children’s Cells Living in Mothers’ Brains
The link between a mother and child is profound, and new research suggests a physical connection even deeper than anyone thought. The profound psychological and physical bonds shared by the mother and her child begin during gestation when the mother is everything for the developing fetus, supplying warmth and sustenance, while her heartbeat provides a soothing constant rhythm.
The physical connection between mother and fetus is provided by the placenta, an organ, built of cells from both the mother and fetus, which serves as a conduit for the exchange of nutrients, gasses, and wastes. Cells may migrate through the placenta between the mother and the fetus, taking up residence in many organs of the body including the lung, thyroid muscle, liver, heart, kidney and skin. These may have a broad range of impacts, from tissue repair and cancer prevention to sparking immune disorders.
It is remarkable that it is so common for cells from one individual to integrate into the tissues of another distinct person. We are accustomed to thinking of ourselves as singular autonomous individuals, and these foreign cells seem to belie that notion, and suggest that most people carry remnants of other individuals. As remarkable as this may be, stunning results from a new study show that cells from other individuals are also found in the brain. In this study, male cells were found in the brains of women and had been living there, in some cases, for several decades. What impact they may have had is now only a guess, but this study revealed that these cells were less common in the brains of women who had Alzheimer’s disease, suggesting they may be related to the health of the brain.