Posts tagged cerebrospinal fluid
Articles and news from the latest research reports.
Mechanism of Parkinson’s spread demonstrated
An international, interdisciplinary group of researchers led by Gabor G. Kovacs from the Clinical Institute of Neurology at the MedUni Vienna has demonstrated, through the use of a new antibody, how Parkinson’s disease spreads from cell to cell in the human brain. Until now, this mechanism has only been observed in experimental models, but has now been demonstrated for the first time in humans too.
At the focus of the study, recently published in the highly respected journal “Neurobiology of Disease”, is the protein α-synuclein. This protein is present in the human brain but develops into a pathologically modified form in the presence of Parkinson’s disease and a common type of age-related dementia (known as Lewy body dementia, responsible for up to a quarter of all dementia-related diseases).
This study, which was carried out by a team from the MedUni Vienna in collaboration with researchers from the USA, Germany and Hungary, demonstrates for the first time that human nerve cells take up the pathological α-synuclein and thereby transfer the disease from one cell to the next. “This explains why patients with Parkinson’s disease deteriorate more and more from a clinical perspective and develop new symptoms, because the disease is able to spread to other parts of the brain through this infection process,” says Gabor G Kovacs, commenting on the central finding of the study.
New antibody achieved major breakthrough
The researchers demonstrated this mechanism using an antibody that scientists from the MedUni Vienna played a key role in helping to develop in collaboration with the German biotech firm Roboscreen. As the study shows, this antibody is the first to distinguish between the physiologically present and disease-associated form of α-synuclein and reacts exclusively with the pathological form.
Mechanism of spread demonstrated for the first time could provide a basis for new treatments for Parkinson’s
"For patients with Parkinson’s disease, this means that α-synuclein’s mechanism of spread from cell to cell could serve as a point of therapeutic attack if we are able to block this cell-to-cell transfer mechanism", continues Kovacs. In diagnostic terms, this antibody also represents a major breakthrough, since the antibodies used previously were unable to distinguish between the physiological and disease-associated form, which meant that they could not be used as easily for diagnostic purposes, e.g. in body fluids.
New antibody improves diagnosis
The fact that this is now possible for the first time has been demonstrated by a further study, also recently published in the specialist publication “Clinical Neuropathology”. According to this study, the new antibody can be used to detect disease-associated α-synuclein in the cerebrospinal fluid of patients with brain disease associated with α-synuclein. This is of major importance for clinical practice, because it means it will be possible to clinically determine whether the dementia is caused by Lewy bodies or not. This study arose through close collaboration between the Clinical Institute of Neurology (Gabor G. Kovacs) and the University Department of Neurology (Walter Pirker) at the MedUni Vienna.
(Source: meduniwien.ac.at)
NIH and Italian Scientists Develop Nasal Test for Human Prion Disease
A nasal brush test can rapidly and accurately diagnose Creutzfeldt-Jakob disease (CJD), an incurable and ultimately fatal neurodegenerative disorder, according to a study by National Institutes of Health scientists and their Italian colleagues.
Up to now, a definitive CJD diagnosis requires testing brain tissue obtained after death or by biopsy in living patients. The study describing the less invasive nasal test appears in the Aug. 7 issue of the New England Journal of Medicine.
CJD is a prion disease. These diseases originate when, for reasons not fully understood, normally harmless prion protein molecules become abnormal and gather in clusters. Prion diseases affect animals and people. Human prion diseases include variant, familial and sporadic CJD. The most common form, sporadic CJD, affects an estimated 1 in one million people annually worldwide. Other prion diseases include scrapie in sheep; chronic wasting disease in deer, elk and moose; and bovine spongiform encephalopathy (BSE), or mad cow disease, in cattle. Scientists have associated the accumulation of these clusters with tissue damage that leaves sponge-like holes in the brain.
“This exciting advance, the culmination of decades of studies on prion diseases, markedly improves on available diagnostic tests for CJD that are less reliable, more difficult for patients to tolerate, and require more time to obtain results,” said Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID), a component of NIH. “With additional validation, this test has potential for use in clinical and agricultural settings.”
An easy-to-use diagnostic test would let doctors clearly differentiate prion diseases from other brain diseases, according to Byron Caughey, Ph.D., the lead NIAID scientist involved in the study. Although specific CJD treatments are not available, prospects for their development and effectiveness could be enhanced by early and accurate diagnoses. Further, a test that identifies people with various forms of prion diseases could help to prevent the spread of prion diseases among and between species. For instance, it is known that human prion diseases can be transmitted via medical procedures such as blood transfusions, transplants and the contamination of surgical instruments. People also have contracted variant CJD after exposure to BSE-infected cattle.
The NIAID study involved 31 nasal samples from patients with CJD and 43 nasal samples from patients who had other neurologic diseases or no neurologic disease at all. These samples were collected primarily by Gianluigi Zanusso, M.D., Ph.D., and colleagues at the University of Verona in Italy, who developed the technique of brushing the inside of the nose to collect olfactory neurons connected to the brain. Testing in Dr. Caughey’s lab in Montana then correctly identified 30 of the 31 CJD patients (97 percent sensitivity) and correctly showed negative results for all 43 of the non-CJD patients (100 percent specificity). By comparison, tests using cerebral spinal fluid—currently used to detect sporadic CJD—were 77 percent sensitive and 100 percent specific, and the results took twice as long to obtain.
Jason Wilham, Ph.D., Christina Orrú, Ph.D., Dr. Caughey, and other members of his research group had previously developed the cerebral spinal fluid test method with Ryuichiro Atarashi, M.D., Ph.D., a former NIAID postdoctoral fellow who is now at Nagasaki University in Japan.
While continuing to validate the test method in CJD patients, Dr. Caughey’s group is looking to expand the study to diagnose forms of prion diseases in sheep, cattle and wildlife. The team continues to collaborate with Dr. Zanusso’s group, which is looking to replace the nasal brush with an even simpler swabbing approach.
Gene variant puts women at higher risk of Alzheimer’s than it does men
Carrying a copy of a gene variant called ApoE4 confers a substantially greater risk for Alzheimer’s disease on women than it does on men, according to a new study by researchers at the Stanford University School of Medicine.
The scientists arrived at their findings by analyzing data on large numbers of older individuals who were tracked over time and noting whether they had progressed from good health to mild cognitive impairment — from which most move on to develop Alzheimer’s disease within a few years — or to Alzheimer’s disease itself.
The discovery holds implications for genetic counselors, clinicians and individual patients, as well as for clinical-trial designers. It could also help shed light on the underlying causes of Alzheimer’s disease, a progressive neurological syndrome that robs its victims of their memory and ability to reason. Its incidence increases exponentially after age 65. An estimated one in every eight people past that age in the United States has Alzheimer’s. Experts project that by mid-century, the number of Americans with Alzheimer’s will more than double from the current estimate of 5-6 million.
According to the Alzheimer’s Association, it is already the nation’s most expensive disease, costing more than $200 million annually. (The epidemiology of mild cognitive impairment is fuzzier, but this gateway syndrome is clearly more widespread than Alzheimer’s.)
Changes in proteins may predict ALS progression
Measuring changes in certain proteins — called biomarkers — in people with amyotrophic lateral sclerosis may better predict the progression of the disease, according to scientists at Penn State College of Medicine.
ALS is often referred to as Lou Gehrig’s disease, is a neurological disease in which the brain loses its ability to control movement as motor neurons degenerate. The course of the disease varies, with survival ranging from months to decades.
"The cause of most cases of ALS remains unknown," said James Connor, Distinguished Professor of Neurosurgery, Neural and Behavioral Sciences and Pediatrics. "Although several genetic and environmental factors have been identified, each accounts for only a fraction of the total cases of ALS."
This clinical variation in patients presents challenges in terms of managing the disease and developing new treatments. Finding relevant biomarkers, which are objective measures that reflect changes in biological processes or reactions to treatments, may help address these challenges.
The project was led by Xiaowei Su, an M.D./ Ph.D. student in Connor’s laboratory, in collaboration with Zachary Simmons, director of the Penn State Hershey ALS Clinic and Research Center. Su studied plasma and cerebrospinal fluid samples previously collected from patients undergoing diagnostic evaluation, who were later identified as having ALS. Analysis shows that looking at multiple biomarkers to predict progression is not only mathematically possible, it improves upon methods using single biomarkers.
Statistical models analyzing plasma had reasonable ability to predict total disease duration and used seven relevant biomarkers. For example, higher levels of the protein IL-10 predict a longer disease duration. IL-10 is involved with anti-inflammation, suggesting that lower levels of inflammation are associated with a longer disease duration.
The researchers identified six biomarkers for cerebrospinal fluid. For example, higher levels of G-CSF — a growth factor known to have protective effects on motor neurons, the cells that die in ALS — predicts a longer disease duration.
Perhaps most importantly, the results suggest that a combination of biomarkers from both plasma and cerebrospinal fluid better predict disease duration.
While the size of this study is small, the ability of the specific biomarkers used to predict prognosis suggests that the approach holds promise.
"The results argue for the usefulness of researching this approach for ALS both in terms of predicting disease progression and in terms of determining the impact of therapeutic strategies," Connor said. "The results present a compelling starting point for the use of this method in larger studies and provide insights for novel therapeutic targets."
(Source: news.psu.edu)
Omega-3 dietary supplements pass the blood-brain barrier
New research from Karolinska Institutet shows that omega-3 fatty acids in dietary supplements can cross the blood brain barrier in people with Alzheimer’s disease, affecting known markers for both the disease itself and inflammation. The findings are presented in the Journal of Internal Medicine, and strengthen the evidence that omega-3 may benefit certain forms of this seriously debilitating disease.
"Earlier population studies indicate that omega-3 can protect against Alzheimer’s disease, which makes it interesting to study the effects of dietary supplements containing this group of fatty acids in patients who have already developed the disease," says the study’s lead author Dr Yvonne Freund-Levi.
Omega-3 and other essential polyunsaturated fatty acids accumulate in the central nervous system (CNS) during gestation. It has been assumed that these acids are continually replaced throughout life, but little is known about how this occurs and whether changes in diet can affect the transport of important fatty acids across the blood-brain barrier. The blood-brain barrier serves to protect the brain from harmful chemicals existing naturally in the blood, but also blocks the delivery of drug substances to the brain.
Several diseases can affect the fatty acid profile of the CNS; in patients with Alzheimer’s disease, for example, previous research has observed lower than normal brain concentrations of docosahexaenoic acid (DHA), an omega-3 fatty acid.
In the present study, part of the larger OmegAD project, scientists examined whether omega-3 dietary supplements change the fatty acid profile of the CNS in patients with mild Alzheimer’s disease. Thirty-three patients participated in the study, 18 of whom received a daily omega-3 supplement and 15 a placebo for six months. The results show that the first group had higher levels of both DHA and eicosapentaenoic acid (EPA, another omega-3 fatty acid) in their cerebrospinal fluid (which surrounds the CNS) and blood. No such change was seen in the placebo group.
Moreover, they also found that levels of DHA correlated directly with the degree of change in Alzheimer’s disease and inflammatory markers in the cerebrospinal fluid. Researchers in the field have long been interested in this link between Alzheimer’s disease and inflammation, but attempts to treat the disease using traditional anti-inflammatory drugs have failed to produce any improvements in memory function.
"In animals, DHA dietary supplements can lead to an increase in DHA concentrations in the CNS," says Professor Jan Palmblad, who initiated the study. "Here we show that the same applies to humans, which suggests that omega-3 fatty acids in dietary supplements cross the blood-brain barrier. However, much work remains to be done before we know how these fatty acids can be used in the treatment of Alzheimer’s disease to halt memory loss."
Multiple Sclerosis Appears to Originate in Different Part of Brain Than Long Believed
The search for the cause of multiple sclerosis, a debilitating disease that affects up to a half million people in the United States, has confounded researchers and medical professionals for generations. But Steven Schutzer, a physician and scientist at Rutgers New Jersey Medical School, has now found an important clue why progress has been slow – it appears that most research on the origins of MS has focused on the wrong part of the brain.
Look more to the gray matter, the new findings published in the journal PLOS ONE suggest, and less to the white. That change of approach could give physicians effective tools to treat MS far earlier than ever before.
Until recently, most MS research has focused on the brain’s white matter, which contains the nerve fibers. And for good reason: Symptoms of the disease, which include muscle weakness and vision loss, occur when there is deterioration of a fatty substance called myelin, which coats nerves contained in the white matter and acts as insulation for them. When myelin in the brain is degraded, apparently by the body’s own immune system, and the nerve fiber is exposed, transmission of nerve impulses can be slowed or interrupted. So when patients’ symptoms flare up, the white matter is where the action in the brain appears to be.
But Schutzer attacked the problem from a different direction. He is one of the first scientists to analyze patients’ cerebrospinal fluid (CSF) by taking full advantage of a combination of technologies called proteomics and high-resolution mass spectrometry. “Proteins present in the clear liquid that bathes the central nervous system can be a window to physical changes that accompany neurological disease,” says Schutzer, “and the latest mass spectrometry techniques allow us to see them as never before.” In this study, he used that novel approach to compare the cerebrospinal fluid of newly diagnosed MS patients with that of longer term patients, as well as fluid taken from people with no signs of neurological disease.
What Schutzer found startled one of his co-investigators, Patricia K. Coyle of Stony Brook University in New York, one of the leading MS clinicians and researchers in the country. The proteins in the CSF of the new MS patients suggested physiological disruptions not only in the white matter of the brain where the myelin damage eventually shows up. They also pointed to substantial disruptions in the gray matter, a different part of the brain that contains the axons and dendrites and synapses that transfer signals between nerves.
Several scientists had in fact hypothesized that there might be gray matter involvement in early MS, but the technology needed to test their theories did not yet exist. Schutzer’s analysis, which Coyle calls “exquisitely sensitive,” provides the solid physical evidence for the very first time. It includes a finding that nine specific proteins associated with gray matter were far more abundant in patients who had just suffered their first attack than in longer term MS patients or in the healthy controls. “This evidence indicates gray matter may be the critical initial target in MS rather than white matter,” says Coyle. “We may have been looking in the wrong area.”
According to Coyle, that realization presents exciting possibilities. One, she says, is that patients who suffer attacks that appear related to MS could have their cerebrospinal fluid tested quickly. If proteins that point to early MS are found, helpful therapy could begin at once, before the disease can progress further.
Coyle says Schutzer’s findings may also lead one day to more effective treatments for MS with far fewer side effects. Without specific knowledge of what causes multiple sclerosis, patients now need to take medications that can broadly weaken their immune systems. These drugs slow the body’s destruction of myelin in the brain, but also degrade the immune system’s ability to keep the body healthy in other ways. By suggesting an exciting new direction for MS research, Schutzer and his team may have set the stage for more targeted treatments that attack MS while preserving other important immune functions.
Schutzer sees an even broader future for the work he is now doing. He also has used advanced analysis of cerebrospinal fluid to identify physical markers for neurological ailments that include Lyme disease, in which he has been a world leader in research for many years, as well as chronic fatigue syndrome. He says, “When techniques are refined, more medical conditions are examined, and costs per patient come down, one day there could be a broad panel of tests through which patients and their doctors can get early evidence of a variety of disorders, and use that knowledge to treat them both more quickly and far more effectively than is possible now. “
New MRI method fingerprints tissues and diseases
A new method of magnetic resonance imaging (MRI) could routinely spot specific cancers, multiple sclerosis, heart disease and other maladies early, when they’re most treatable, researchers at Case Western Reserve University and University Hospitals (UH) Case Medical Center suggest in the journal Nature.
Each body tissue and disease has a unique fingerprint that can be used to quickly diagnose problems, the scientists say.
By using new MRI technologies to scan for different physical properties simultaneously, the team differentiated white matter from gray matter from cerebrospinal fluid in the brain in about 12 seconds, with the promise of doing this much faster in the near future.
The technology has the potential to make an MRI scan standard procedure in annual check-ups, the authors believe. A full-body scan lasting just minutes would provide far more information and require no radiologist to interpret the data, making diagnostics cheap, compared to today’s scans, they contend.
"The overall goal is to specifically identify individual tissues and diseases, to hopefully see things and quantify things before they become a problem," said Mark Griswold, a radiology professor at Case Western Reserve School of Medicine and UH Case Medical Center. "But to try to get there, we’ve had to give up everything we knew about the MRI and start over."
Griswold has been working on this goal with Case Western Reserve’s Vikas Gulani, MD, an assistant professor of radiology, and Nicole Seiberlich, assistant professor of biomedical engineering, for a decade. During the last three years, they developed the technology and proved the concept with graduate student Dan Ma; Kecheng Liu, PhD, collaborations manager from Siemens Medical Solutions Inc.; Jeffrey L. Sunshine, MD, professor of radiology and a radiologist at UH Case Medical Center; and Jeffrey L. Duerk, dean of Case School of Engineering and professor of biomedical engineering.
(Image: Rex Features)
Biomarkers in Cerebrospinal Fluid Can Identify Patients with Alzheimer´s disease
Analysis of specific biomarkers in a cerebrospinal fluid sample can differentiate patients with Alzheimer’s disease from those with other types of dementia. The method, which is being studied by researchers at Sahlgrenska Academy, may eventually permit earlier detection of Alzheimer’s disease.
Due to the similarity of the symptoms, differentiating patients with Alzheimer’s from those with other types of dementia – or patients with Parkinson disease from those with other motor disorders – is often difficult.
Making a proper diagnosis is essential if proper treatment and medication are to commence at an early stage. A research team at Sahlgrenska Academy, University of Gothenburg, is developing a new method to differentiate patients with Alzheimer’s disease or Parkinson disease by analyzing a cerebrospinal fluid sample.
The study, led by Professor Kaj Blennow and conducted among 450 patients at Skåne University Hospital and Sahlgrenska University Hospital, involved testing five proteins that serve as biomarkers for the two diseases.
“Previous studies have shown that Alzheimer’s disease is associated with biochemical changes in specific proteins of the brain,” says Annika Öhrfelt, a researcher at Sahlgrenska Academy. “This study has found that the inclusion of a new protein can differentiate patients with Alzheimer’s disease from those with Lewy body dementia, Parkinson disease dementia and other types of dementia.”
Similarly, the biomarkers can differentiate patients with Parkinson disease from those with atypical Parkinsonian disorders.
“Additional studies are needed before the biomarkers can be used in clinical practice during the early stages of disease,” says Öhrfelt, “but these results represent an important step along the way.”
(Source: alphagalileo.org)