Posts tagged biomarkers

Scientists at Washington University School of Medicine in St. Louis have helped identify many of the biomarkers for Alzheimer’s disease that could potentially predict which patients will develop the disorder later in life. Now, studying spinal fluid samples and health data from 201 research participants at the Charles F. and Joanne Knight Alzheimer’s Disease Research Center, the researchers have shown the markers are accurate predictors of Alzheimer’s years before symptoms develop.

“We wanted to see if one marker was better than the other in predicting which of our participants would get cognitive impairment and when they would get it,” said Catherine Roe, PhD, research assistant professor of neurology. “We found no differences in the accuracy of the biomarkers.”

The study, supported in part by the National Institute on Aging, appears in Neurology.

The researchers evaluated markers such as the buildup of amyloid plaques in the brain, newly visible thanks to an imaging agent developed in the last decade; levels of various proteins in the cerebrospinal fluid, such as the amyloid fragments that are the principal ingredient of brain plaques; and the ratios of one protein to another in the cerebrospinal fluid, such as different forms of the brain cell structural protein tau.

The markers were studied in volunteers whose ages ranged from 45 to 88. On average, the data available on study participants spanned four years, with the longest recorded over 7.5 years.

The researchers found that all of the markers were equally good at identifying subjects who were likely to develop cognitive problems and at predicting how soon they would become noticeably impaired.

Next, the scientists paired the biomarkers data with demographic information, testing to see if sex, age, race, education and other factors could improve their predictions.

“Sex, age and race all helped to predict who would develop cognitive impairment,” Roe said. “Older participants, men and African Americans were more likely to become cognitively impaired than those who were younger, female and Caucasian.”

Roe described the findings as providing more evidence that scientists can detect Alzheimer’s disease years before memory loss and cognitive decline become apparent.

“We can better predict future cognitive impairment when we combine biomarkers with patient characteristics,” she said. “Knowing how accurate biomarkers are is important if we are going to some day be able to treat Alzheimer’s before symptoms and slow or prevent the disease.”

Clinical trials are already underway at Washington University and elsewhere to determine if treatments prior to symptoms can prevent or delay inherited forms of Alzheimer’s disease. Reliable biomarkers for Alzheimer’s should one day make it possible to test the most successful treatments in the much more common sporadic forms of Alzheimer’s.

(Source: news.wustl.edu)

Exosomes are small, virus-like particles that can transport genetic material and signal substances between cells. Researchers at Lund University, Sweden, have made new findings about exosomes released from aggressive brain tumours, gliomas. These exosomes are shown to have an important function in brain tumour development, and could be utilised as biomarkers to assess tumour aggressiveness through a blood test.

“Current wisdom says that cells are closed entities that communicate through the secretion of soluble signalling molecules. Recent findings indicate that cells can exchange more complex information – whole packages of genetic material and signalling proteins. This is an entirely new conception of how cells communicate”, says Dr Mattias Belting, Professor of Oncology at Lund University and senior consultant in oncology at Skåne University Hospital, Lund, Sweden.

Exosomes are small vesicles of only 30–90 nm. They are produced inside cells and act as “transport vehicles” of genetic material that can be transferred to surrounding cells. Since their first discovery, exosomes have been found in blood, saliva, urine, breast milk and other body fluids.

Mattias Belting’s research group has investigated exosomes released from tumour cells of patients with gliomas. The tiny exosome particles are delivered from the tumour to healthy cells of the brain and may prime normal tissue for efficient spreading of the tumour. The researchers in Lund have now shown that the aggressiveness of the tumour is reflected in the exosome molecular profile.

“We have succeeded in developing a method for the isolation of exosomes from brain tumour patients through a relatively simple blood test. Our analyses indicate that the content of exosomes mirrors the aggressiveness of the tumour in a unique manner”, says postdoctoral researcher Paulina Kucharzewska.

Exosomes could thus be utilised as biomarkers, i.e. to provide guidance on how the patient should be treated and to monitor treatment response. This possibility is particularly attractive with brain tumours that are not readily accessible for tissue biopsy. However, analysis of exosomes from the blood may also prove important with other tumour types. The value of conventional tumour biopsies is limited by the heterogeneity of tumour tissue, i.e. the tissue specimen may not be fully representative of the biological characteristics of a particular tumour. Exosomes, however, may offer more comprehensive information, according to the researchers.

The second international meeting on exosomes has just opened in Boston, and Mattias Belting and members of his team are there.

“It is very exciting to be part of the emergence of a novel research field. It can be anticipated that the most influential researchers in this area may one day be awarded the Nobel Prize”, says Dr Belting.

The results are published in Proceedings of the National Academy of Sciences (PNAS).

(Source: lunduniversity.lu.se)

Autism spectrum disorders (ASD) are neurodevelopmental disorders typically characterized by difficulties in social interactions and delayed or abnormal language development. Although ASD reportedly affects 1 in 88 people in the United States, to date there have been no distinctive biomarkers to diagnose the disease. In a special themed issue of Disease Markers, investigators report on the current understanding of ASD genetics and the possibilities of translating genetic research toward biomarker development in ASD.

"Although some individuals with ASD are highly functional, many are severely impaired and require permanent care. The significant level of impairment combined with the fact that no specific therapy is yet available for ASD, make ASD a devastating illness for patients and families, and a heavy financial burden for the healthcare system," says guest editor, Irina Voineagu, MD, PhD, RIKEN Omics Science Center, Yokohama, Japan. "The most effective intervention for ASD has proven to be early behavioral therapy. Thus the identification of biological markers for ASD, allowing very early detection, even before the onset of symptoms, would be of tremendous value."

Five articles comprise this comprehensive issue, providing an overview of ASD genetic models, an exploration of several key emerging concepts in understanding ASD’s molecular basis, and discussion of current biomarker development, focusing on genomic data.

Following an introduction by Voineagu, Yuri Bozzi and colleagues review the phenotype characteristics of currently available mouse models of ASD. Carmen Panaitof then discusses the role of the songbird as an experimental model system for investigating the genetic basis of human language and its ASD-related impairments. Michael Bowers and Genevieve Konopka further explore language deficits and provide new evidence for the role of the FOXP gene to regulate language. Alka Saxena, Dave Tang, and Piero Carninci focus on the functional roles of the gene MECP2, which is mutated in most cases of Rett syndrome, one of the ASDs.

A review rounding out the issue is “Subphenotype-Dependent Disease Markers for Diagnosis and Personalized Treatment of Autism Spectrum Disorders,” by Valerie W. Hu, PhD, The George Washington University, School of Medicine and Health Sciences, Washington, DC, PhD, which discusses current progress toward identifying ASD biomarkers based on genome-wide data.

"Without genetic or molecular markers for screening, individuals with ASD are typically not diagnosed before the age of 2, with milder cases diagnosed much later," writes Dr. Hu. "Because early diagnosis is tantamount to early behavioral intervention, which has been shown to improve individual outcomes, an objective biomarker test that can diagnose at-risk children perinatally is a medical imperative."

Hu demonstrates the possibility and importance of developing ASD subtypes to help identify relevant disease markers, which can ultimately aid in developing specific targeted therapies.

Voineagu concludes, “It is exciting times for genetic research and although the phenotypic and genetic heterogeneity of ASD often seem to be a daunting conundrum, well-defined diagnostic criteria, larger cohort sizes for genetic studies and integrative approaches of genomic and epigenomic data already delineate a promising avenue for elucidating the mechanisms of ASD.”

(Source: eurekalert.org)

There is a long history of research on impaired eye movements associated with schizophrenia. Using a series of simple viewing tests, researchers of a new paper in Biological Psychiatry explored the ability of these eye movement tests to distinguish people with and without the diagnosis of schizophrenia.

Using their complete dataset, they were able to develop a model that could discriminate all schizophrenia cases from healthy control subjects with an impressive 98.3% accuracy.

Drs. Philip Benson and David St. Clair, lead authors on the paper, agreed that their findings were remarkable: “It has been known for over a hundred years that individuals with psychotic illnesses have a variety of eye movement abnormalities, but until our study, using a novel battery of tests, no one thought the abnormalities were sensitive enough to be used as potential clinical diagnostic biomarkers.”

Their battery of tests included smooth pursuit, free-viewing, and gaze fixation tasks. In smooth pursuit, people with schizophrenia have well-documented deficits in the ability to track slow-moving objects smoothly with their eyes. Their eye movements tend to fall behind the moving object and then catch-up with the moving object using a rapid eye movement, called a saccade.. A picture is displayed in the free-viewing test, and where most individuals follow a typical pattern with their gaze as they scan the picture, those with schizophrenia follow an abnormal pattern. In a fixation task, the instruction is to keep a steady gaze on a single unmoving target, which tends to be difficult for individuals with schizophrenia.

As expected, the researchers found that the performance of individuals with schizophrenia was abnormal compared to the healthy volunteer group on each of the eye tests. At right is an example of the differences, with the eye tracking of a schizophrenia case in red and a healthy control in blue.

The researchers then used several methods to model the data. The accuracy of each of the created algorithms was then tested by using eye test data from another group of cases and controls. Combining all the data, one of the models achieved 98.3% accuracy.

"It is encouraging to see the high sensitivity of this model for the diagnosis of schizophrenia. It will be interesting to see the extent to which this approach enables clinical investigators to distinguish people with schizophrenia from individuals with other psychiatric disorders," commented Dr. John Krystal, Editor of Biological Psychiatry.

Benson and St Clair have already started that work, stating, “We now have exciting unpublished data showing that patterns of eye movement abnormalities are specific to different psychiatric subgroups, another key requirement for diagnostic biomarkers. The next thing we want to know is when the abnormalities are first detectable and can they be used as disease markers for early intervention studies in major mental illness?”

"We are also keen to explore how best our findings can be developed for use in routine clinical practice," they added. Typical neuropsychological assessments are time-consuming, expensive, and require highly trained individuals to administer. In comparison, these eye tests are simple, cheap, and take only minutes to conduct. This means that a predictive model with such precision could potentially be incorporated in clinics and hospitals to aid physicians by augmenting traditional symptom-based diagnostic criteria.

(Source: alphagalileo.org)

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)