LONDON – British scientists have developed a preliminary blood test that could one day be used to detect the proteins that cause the human form of mad cow disease, according to a new study.

The disease-carrying proteins, or prions, that cause variant Creutzfeldt-Jakob disease can remain dormant for decades and there are currently no reliable tests to detect them. after the mad cow scare that hit Britain in the 1980s, some experts fear there might be thousands of hidden cases in the country. the department of health estimates one in 4,000 Britons could be infected.

In a study published Thursday in the medical journal Lancet, scientists describe a new blood test that can identify tiny amounts of the prions that cause mad cow disease. John Collinge of the U.K. Medical Research Council Prion Unit and colleagues used their test on 190 blood samples, including 21 people with symptoms of the brain-wasting disease.

The new test correctly identified mad cow disease in 15 patients and was better at picking up small concentrations of the disease-causing proteins than the currently available test. the scientists thought their test might have missed the other six patients because the patients’ levels of prion-causing disease were too low.

“Our findings demonstrate the ability to detect prion infection in blood and show that a donor screening test is technically feasible,” Collinge and colleagues wrote. Mad cow disease can be spread by blood transfusions, surgery or dental procedures. Some experts have called for better ways to protect the population from the degenerative disease.

Variant Creutzfeldt-Jakob disease is usually seen in people who have eaten food products from infected cattle. Patients develop psychiatric symptoms including depression, schizophrenia or psychosis. Most are immobile or mute by the time the disease kills them.

In an accompanying commentary, Luisa Gregori of the U.S. Food and Drug Administration wrote that Collinge and colleagues’ test “represents an important step” towards a diagnostic test for human mad cow disease.

But she warned that for a test to effectively screen large numbers of blood donors, it would need to be much more accurate and capable of detecting the disease in people carrying the disease who did not already have symptoms.

Published on Mon Jan 17 09:20:59 GMT 2011

“A new technique could lead to a blood test for detecting Alzheimer’s,” BBC News reported.

This news story is based on research that has developed a new method to screen blood for antibodies, a range of proteins that the body creates in response to specific diseases. The technique involved passing blood samples over special slides coated with a synthetic substance designed to identify antibodies found only in people with a specific disease. Researchers first refined the test in mice and then focused on Alzheimer’s disease in humans. They found that there were raised levels of two antibodies in the blood of 16 people with Alzheimer’s disease but not in 14 unaffected people.

This promising technique may eventually lead to blood tests for conditions such as Alzheimer’s disease. however, this research is in its early stages and now needs testing in much larger groups of people to confirm that these two antibodies are actual markers of Alzheimer’s. Additionally, the study did not determine at what point in the disease levels of these antibodies become raised, so we cannot presently tell if it can detect early-stage Alzheimer’s disease.

The study was carried out by researchers from the Scripps Research institute in Florida and was funded by the US National Institutes of Health. it was published in Cell, a peer-reviewed scientific journal.

This research was generally covered adequately by the media, with most newspapers highlighting the preliminary nature of the research. however, as yet, the researchers have not determined how early in the course of Alzheimer’s disease the antibody changes could be detected. at present, it is not possible to say whether this test would be able to detect Alzheimer’s disease any earlier than current diagnostic tests, as some newspapers have prematurely suggested.

When the body mounts an immune response to disease or infection, it may produce antibodies. These are specific proteins that help the body neutralise the threat it has encountered. Once antibodies are created to deal with a specific illness or substance, the body can easily reproduce them if exposed again. This is why previously having an illness or receiving a vaccination can provide increased immunity. Substances that cause us to produce antibodies are called antigens, and can include proteins, foreign cells and bacteria.

This laboratory study developed a potential method to screen for the immune response to various diseases using slides covered in special synthetic chemicals, which would show the presence of antibodies consistent with specific diseases. The technique was then tested to determine whether it could find a difference in the antibodies produced by people with Alzheimer’s disease and by healthy control subjects. usually, diagnosis of Alzheimer’s disease requires a series of cognitive tests and the exclusion of other causes through brain imaging. it can only be confirmed by looking at changes in the brain after death.

To find antibodies that may be relevant to diseases, researchers currently use libraries of antigens. By passing blood over these, they can detect whether an individual has relevant antibodies as these will bind to the appropriate antigen. however, when screening for new antibodies that may be produced in a particular disease, this approach is not especially useful as the antigens being screened for are selected based on the likelihood that they play a role in the disease. Additionally, some proteins involved in different diseases are normally produced by the body, meaning the body would not have produced any antibodies against them. however, if normal proteins undergo changes to become the “disease form” of the protein, this may trigger an immune response.

To search for antibodies, the researchers used unnatural synthetic molecules called “peptoids”. These peptoids can form shapes that cannot be made by normal unmodified proteins but may mimic some aspects of the shape of disease proteins, allowing them to bind to antibodies specifically created in response to certain diseases.

The researchers made 4,608 synthetic peptoids of varying shapes and fixed their position on microscope slides. They then took blood from a mouse that had been treated with chemicals to make it develop symptoms resembling multiple sclerosis (MS). MS affects the nervous system, in which an immune response is thought to contribute to the disease’s progression.

The blood was passed over the microscope slide so that the antibodies in the blood could bind to the peptoids. The researchers then used a secondary antibody, which would bind to any mouse antibodies that had bound to the various peptoids on the slide. The secondary antibody was fluorescent so it could be visually detected.

The researchers used this initial experiment to optimise the concentration of blood and to find some peptoids that had bound antibodies. They then used the slides to compare blood from the mice with MS to blood from normal, control mice. if there were areas on the slide where bonding had occurred using MS mouse blood but not control mouse blood, it might indicate antibodies that were specifically produced in response to the MS-like condition.

The researchers then continued their experiments in humans, looking at whether they could see a difference between blood samples from people with Alzheimer’s disease and those of healthy elderly people. They took stored blood samples from six people with Alzheimer’s disease (three of whom had had their Alzheimer’s confirmed following autopsy) and six age-matched, healthy controls. The researchers passed the blood samples over a slide containing 15,000 peptoids. To make sure that any result was specific for Alzheimer’s disease, they also analysed six samples from people with Parkinson’s disease.

After using the screening technique to initially to find peptoids that bound antibodies from people with Alzheimer’s but not controls, the researchers repeated the test in an additional 16 Alzheimer’s samples, 14 controls and six people with lupus (an immune disease).

In the mouse model of MS, the researchers found that an antibody binding to three peptoids, which they named AMogP1-3, could differentiate between healthy mice and mice with MS-like symptoms. They were able to determine that the antibody that bound to the AMogP1-3 peptoids was the antibody that bound to a protein called Mog. Injection with the Mog protein had been used to cause MS symptoms in the mice. This was a proof of concept that use of an unnatural molecule could confirm the presence of an antibody that recognises a disease-triggering protein.

For the Alzheimer’s screening, the researchers chose three spots on the slide which had the greatest fluorescent signal (indicating that lots of antibodies had bound). These sites contained three peptoids that distinguished the people with Alzheimer’s from the controls. The researchers named the peptoids AD peptoids (ADP) 1-3. at least three times as many antibodies had bound in the Alzheimer’s samples compared to the control samples.

In the larger sample of Alzheimer’s and controls, the researchers found that the sensitivity (percentage of Alzheimer’s samples correctly identified as having Alzheimer’s) was 93.7% and the specificity (percentage of control samples correctly identified as control samples) was between 93.7% and 100% for each of the peptoids.

They found that ADP1 and ADP3 bound to the same antibody, while ADP2 bound to a different antibody.

The researchers said that their new approach did not require them to identify a specific antigen to screen for antibodies that are raised in disease. rather, by using a large collection of unnatural molecules, some of which may happen to have the right shape to bind to an antibody, they were able to carry out a high level of screening in samples of people with disease compared to controls.

They said that for Alzheimer’s samples, their “preliminary study is promising as it represents a high level of diagnostic sensitivity and specificity, at least within the relatively limited range of samples analyzed”. However, they pointed out that “more work will be required before it is clear whether the peptoids ADP1-3 will be useful for the clinical diagnosis of Alzheimer’s disease”.

This research has applied a novel approach to antibody screening, using slides coated with thousands of synthetic molecules to screen blood samples for antibodies associated with specific diseases. This well-conducted preliminary research may potentially provide a new method to screen for the presence antibodies that may be characteristic of a disease, and may also aid diagnostics.

When tested in a small number of blood samples from people with Alzheimer’s disease and healthy controls, the researchers’ method could clearly discriminate between the two groups and found higher levels of two antibodies in the Alzheimer’s samples compared to the controls.

While this interesting work could theoretically screen for a range of conditions, the researchers rightly highlight the preliminary nature of their study and emphasise that more work is needed before this could be a diagnostic test for Alzheimer’s or any other disease. In particular, they say:

• There is now the need for analysis of samples from a larger number of patients from a more diverse population.
• The samples came from people who had a confirmed diagnosis of Alzheimer’s disease. it is important to test samples from patients who have milder cognitive impairment that subsequently progresses to Alzheimer’s disease to see whether it is possible to use this test for early detection of Alzheimer’s disease.
• While the test can identify the presence of antibodies consistent with a particular disease, it cannot identify which antigens the antibody is designed to neutralise. Therefore, the technique cannot determine which proteins may cause or contribute to the development of a disease.

Overall, this is promising research that may lead to a blood test for Alzheimer’s and other diseases, although it is still at an early stage. To progress, the technique will need further validation in much larger groups of people.

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ScienceDaily (Dec. 8, 2010) — a more sensitive version of a blood test typically used to confirm that someone is having a heart attack could indicate whether a seemingly healthy, middle-aged person has unrecognized heart disease and an increased risk of dying, UT Southwestern Medical Center researchers have found.

In a study available online and in the Dec. 8 print issue of the Journal of the American Medical Association, researchers found that a new, highly sensitive test for a protein called cardiac troponin T (cTnT) could detect the protein in about 25 percent of blood samples supplied by more than 3,500 individuals. the study also found that people with detectable levels of troponin T were nearly seven times more likely to die within six years from heart disease.

"this test is among the most powerful predictors of death in the general population we’ve seen so far," said Dr. James de Lemos, associate professor of internal medicine at UT Southwestern and lead author of the study. "It appears that the higher your troponin T, the more likely you are to have problems with your heart, and the worse you’re going to do, regardless of your other risk factors."

Although previous work has shown an association between cTnT levels and heart disease, standard tests for the protein can detect cTnT in only a very small percentage of the population, limiting the test’s utility for assessing risk in people with no symptoms of heart disease.

The more sensitive test, however, can detect circulating cTnT levels in almost everyone with chronic heart failure and chronic coronary artery disease.

"Because this test seems to identify cardiovascular problems that were previously unrecognized, we hope in the future to be able to use it to prevent some death and disability from heart failure and other cardiac diseases," Dr. de Lemos said.

Emergency room doctors commonly use the standard, less sensitive test for cTnT to determine whether a patient experiencing chest pains is having a heart attack. Dr. de Lemos said the ability to detect lower levels of the protein could make emergency room physicians rethink the interpretation of the cTnT level.

"With the new highly sensitive assays, it’s going to be much more difficult to determine if elevated levels of troponin T are due to a heart attack or rather another chronic form of disease," he said.

The current work with cTnT built on previous findings by Dr. de Lemos from the Dallas Heart Study, a groundbreaking investigation of cardiovascular disease that first involved more than 6,100 Dallas County residents. as part of that study, researchers found that cTnT could be detected with the standard technology in 1 percent of the population.

To determine if newer, more sensitive technology could detect cTnT at lower levels, researchers used the same population of residents. Starting in the year 2000, more than 3,500 participants provided blood samples and underwent multiple body scans with magnetic resonance imaging and computed tomography to examine the heart and other organs. Researchers then tracked the cause and time of death of participants, ages 30 to 65, through 2007.

"this study was designed to be representative of urban communities throughout the United States where there is a high prevalence of obesity, untreated hypertension and diabetes — just as there is in Dallas," Dr. de Lemos said.

Older adults, males, African-Americans and individuals with abnormal thickening or weakness of the heart muscles had the highest levels of cTnT.

The outcomes were validated in a companion paper published in the same print issue of JAMA. the second study, co-authored by Dr. de Lemos and led by Dr. Christopher deFilippi of the University of Maryland School of Medicine, also used the highly sensitive test, but only in participants older than 65. That study found that in addition to death, cTnT was associated with heart failure, and that the risk of both outcomes shifted in concordance with change in cardiac troponin T levels over time.

Other UT Southwestern researchers involved in the study were Dr. Mark Drazner, professor of internal medicine; Colby Ayers, biostatistical consultant in internal medicine; Dr. Amit Khera, assistant professor of internal medicine; Dr. Anand Rohatgi, assistant professor of internal medicine; Dr. Ibrahim Hashim, professor of pathology; Dr. Jarett Berry, assistant professor of internal medicine; Dr. Sandeep Das, assistant professor of internal medicine; and Dr. Darren McGuire, associate professor of internal medicine. Researchers from the University of Oslo and Brigham and Women’s Hospital also participated in the research.

The research was funded by the Donald W. Reynolds Foundation and by the National Institutes of Health. the present study also was supported by Roche Diagnostics.

Disclaimer: this article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

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the above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by UT Southwestern Medical Center.

Journal Reference:

1. J. a. de Lemos, M. H. Drazner, T. Omland, C. R. Ayers, a. Khera, a. Rohatgi, I. Hashim, J. D. Berry, S. R. Das, D. a. Morrow, D. K. McGuire. Association of Troponin T Detected With a Highly Sensitive Assay and Cardiac Structure and Mortality Risk in the General Population. JAMA: the Journal of the American Medical Association, 2010; 304 (22): 2503 DOI: 10.1001/jama.2010.1768

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ScienceDaily (Aug. 18, 2010) — B vitamins-B-6, B-12 and folate-all nourish the brain. but much remains to be discovered about the relation between these essential nutrients and our brainpower.

U.S. Department of Agriculture (USDA) nutritionist Lindsay H. Allen has collaborated in ongoing research that has taken a closer look at the role these nutrients may play in preventing decline in brain function. The investigations, led by Mary N. Haan of the University of California-San Francisco, are part of the multiyear Sacramento (Calif.) Area Latino Study on Aging, or "SALSA." Begun in 1996, the study attracted nearly 1,800 Hispanic seniors, ages 60 to 101, as volunteers.

According to Allen, the research is needed because many studies of B vitamins and brain function have given inconsistent or conflicting results. Allen is director of the Agricultural Research Service (ARS) Western Human Nutrition Research Center in Davis, Calif. ARS is the chief intramural scientific research agency of USDA. Scientists from the University of California-Davis (UCD) and the UCD Medical Center also are collaborating in the research.

An analysis of volunteers’ blood samples showed that lower levels of one B vitamin, folate, were associated with symptoms of dementia and poor brain function, also called "cognitive decline," as determined by standard tests of memory and other factors. The impairments were detectable even though less than 1 percent of the volunteers were actually deficient in folate.

In women, but not men, low levels of folate were associated with symptoms of depression. in fact, female volunteers whose plasma folate levels were in the lowest third were more than twice as likely to have symptoms of depression as volunteers in the highest third. That finding provided new evidence of an association between lower blood folate and depression. Depression is already known to affect brain function.

In research with vitamin B-12, the SALSA team determined that a protein known as holoTC, short for holotranscobalamin, might be key to a new approach for detecting cognitive decline earlier and more accurately.

The researchers have published these and other findings, beginning in 2003 and continuing through this year, in the American Journal of Clinical Nutrition, Clinical Chemistry and Laboratory Medicine, The European Journal of Clinical Nutrition, The Journal of Nutrition, and The Journal of Nutrition, Health, and Aging.

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The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by USDA/Agricultural Research Service. The original article was written by Marcia Wood.

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