The possibility of an inexpensive, convenient test for Alzheimer’s disease has been on the horizon for several years, but previous research leads have been hard to duplicate.
In a study, scientists have taken a step toward developing a blood test for Alzheimer’s, finding a group of markers that hold up in statistical analyses in three independent groups of patients.
‘Reliability and failure to replicate initial results have been the biggest challenge in this field,’ says lead author William Hu, MD, PhD, assistant professor of neurology at Emory University School of Medicine. ‘We demonstrate here that it is possible to show consistent findings.’
Hu and his collaborators at the University of Pennsylvania and Washington University, St. Louis, measured the levels of 190 proteins in the blood of 600 study participants at those institutions. Study participants included healthy volunteers and those who had been diagnosed with Alzheimer’s disease or mild cognitive impairment (MCI). MCI, often considered a harbinger for Alzheimer’s disease, causes a slight but measurable decline in cognitive abilities.
A subset of the 190 protein levels (17) were significantly different in people with MCI or Alzheimer’s. When those markers were checked against data from 566 people participating in the multicenter Alzheimer’s Disease Neuroimaging Initiative, only four markers remained: apolipoprotein E, B-type natriuretic peptide, C-reactive protein and pancreatic polypeptide.
Changes in levels of these four proteins in blood also correlated with measurements from the same patients of the levels of proteins [beta-amyloid] in cerebrospinal fluid that previously have been connected with Alzheimer’s. The analysis grouped together people with MCI, who are at high risk of developing Alzheimer’s, and full Alzheimer’s.
‘We were looking for a sensitive signal,’ says Hu. ‘MCI has been hypothesised to be an early phase of AD, and sensitive markers that capture the physiological changes in both MCI and AD would be most helpful clinically.’
‘The specificity of this panel still needs to be determined, since only a small number of patients with non-AD dementias were included,’ Hu says. ‘In addition, the differing proportions of patients with MCI in each group make it more difficult to identify MCI- or AD-specific changes.’
Neurologists currently diagnose Alzheimer’s disease based mainly on clinical symptoms. Additional information can come from PET brain imaging, which tends to be expensive, or analysis of a spinal tap, which can be painful.
‘Though a blood test to identify underlying Alzheimer’s disease is not quite ready for prime time given today’s technology, we now have identified ways to make sure that a test will be reliable,’ says Hu. ‘In the meantime, the combination of a clinical exam and cerebrospinal fluid analysis remains the best tool for diagnosis in someone with mild memory or cognitive troubles.’ EurekAlert

New research reveals a shared genetic susceptibility to epilepsy and migraine. Findings indicate that having a strong family history of seizure disorders increases the chance of having migraine with aura (MA).
Medical evidence has established that migraine and epilepsy often co-occur in patients; this co-occurrence is called ‘comorbidity.’ Previous studies have found that people with epilepsy are substantially more likely than the general population to have migraine headache. However, it is not clear whether that comorbidity results from a shared genetic cause.
‘Epilepsy and migraine are each individually influenced by genetic factors,’ explains lead author Dr. Melodie Winawer from Columbia University Medical Center in New York. ‘Our study is the first to confirm a shared genetic susceptibility to epilepsy and migraine in a large population of patients with common forms of epilepsy.’
For the present study, Dr. Winawer and colleagues analysed data collected from participants in the Epilepsy Phenome/Genome Project (EPGP)—a genetic study of epilepsy patients and families from 27 clinical centres in the U.S., Canada, Argentina, Australia, and New Zealand. The study examined one aspect of EPGP: sibling and parent-child pairs with focal epilepsy or generalised epilepsy of unknown cause. Most people with epilepsy have no family members affected with epilepsy. EPGP was designed to look at those rare families with more than one individual with epilepsy, in order to increase the chance of finding genetic causes of epilepsy.
Analysis of 730 participants with epilepsy from 501 families demonstrated that the prevalence of MA—when additional symptoms, such as blind spots or flashing lights, occur prior to the headache pain— was substantially increased when there were several individuals in the family with seizure disorders. EPGP study participants with epilepsy who had three or more additional close relatives with a seizure disorder were more than twice as likely to experience MA than patients from families with fewer individuals with seizures. In other words, the stronger the genetic effect on epilepsy in the family, the higher the rates of MA. This result provides evidence that a gene or genes exist that cause both epilepsy and migraine.
Identification of genetic contributions to the comorbidity of epilepsy with other disorders, like migraine, has implications for epilepsy patients. Prior research has shown that coexisting conditions impact the quality of life, treatment success, and mortality of epilepsy patients, with some experts suggesting that these comorbidities may have a greater impact on patients than the seizures themselves. In fact, comorbid conditions are emphasised in the National Institutes of Health Epilepsy Research Benchmarks and in a recent report on epilepsy from the Institute of Medicine.
‘Our study demonstrates a strong genetic basis for migraine and epilepsy, because the rate of migraine is increased only in people who have close (rather than distant) relatives with epilepsy and only when three or more family members are affected,’ concludes Dr. Winawer. ‘Further investigation of the genetics of groups of comorbid disorders and epilepsy will help to improve the diagnosis and treatment of these comorbidities, and enhance the quality of life for those with epilepsy.’ Columbia University Medical Center

Researchers Patricia A. Champion and Matthew Champion from the University of Notre Dame’s Eck Institute for Global Health have developed a method to directly detect bacterial protein secretion, which could provide new insights into a variety of diseases including tuberculosis.
The Champions point out that bacteria use a variety of secretion systems to transport proteins beyond their cell membranes in order to interact with their environment. For bacterial pathogens such as TB, these systems transport bacterial proteins that promote interaction with host cells, leading to virulent disease.
Previously, researchers have relied on methods that have fused enzymes or fluorescent markers to bacterial proteins to identify bacterial genes that are used to export bacterial proteins into host cells. However, these methods can’t be used in the analysis of all bacterial secretion systems, which has limited understanding of the mechanisms that bacteria use to interact with host cells.
The Champions developed a modified form of bacterial proteomics using a MALDI-TOF mass spectrometer, which directly detects the proteins from whole colonies by ionising them with a laser. This research revealed that the method was able to specifically monitor a specialised form of protein secretion, which is a major virulence determinant in both mycobacterial pathogens, such as TB, and Gram-positive pathogens, such as Bacillus and Staphylococcus species.
The Champions demonstrated that this new method is applicable to the study of other bacterial protein export systems that could not be effectively studied under previous methods. Their method could also help in the identification of compounds that can inhibit bacterial protein secretion.
The method’s importance can be seen in the fact that there are approximately 2 million fatal TB cases each year, mostly in the developing world. Also, antibiotic-resistant strains of TB are appearing increasingly. University of Notre Dame

Many diseases, including cancers, leave genetic clues in the body just as criminals leave DNA at the scene of a crime. But tools to detect the DNA-like sickness clues known as miRNAs, tend to be slow and expensive. Now a chemist and a biologist from University of Copenhagen have invented a method that promises to shave days off the lab work done to reveal diseases, using cheap methods and easy to use analytical apparatuses.
Chemistry researcher Tom Vosch and plant molecular biologist Seong Wook Yang invented a DNA sensor, coupling genetic material to a luminous molecule which goes dark only in the presence of a specific target. Details on their invention,
‘
It’s an unusually quick and elegant method for screening
‘We invented a probe that emits light only as long as the sample is clean. That is an unusually elegant and easy way to screen for a particular genetic target’, says Vosch of the Department of Chemistry’s Nano Science Centre.
You could say that the inventors took their cue from crime detection. In murder cases police technicians use DNA to identify the killer. Similarly Individuals with disease are likely to have a unique miRNA profile. Any disease that is attacking a patient leaves this genetic clue all over the victim. And because the profiles of miRNAs vary by type of cancer, finding it proves beyond a reasonable doubt what made the patient sick.
The new detection method exploits a natural quality of genetic material. A single DNA strand is made up of molecules, so called bases, ordered in a unique combination. When two strands join to form their famous double helix, they do so by sticking to complementary copies of themselves. Likewise strands tailored to match particular miRNAs will stick to the real thing with uncanny precision. But detecting this union of the strands was only made possible when Vosch and Yang paired their skills.
Tom Vosch is specialised in studying molecules that light up. Seong Wook Yang is specialised in miRNA. Together they figured out how to attach the light emitting molecules to DNA sensors for miRNA detection. Vosch and Yang discovered, that when these luminous DNA-strands stick with microRNA-strands, their light is snuffed out, giving a very visible indication that the target miRNA is present in the sample. In other words: When the light goes out, the killer is in the house.
Vosch and Yang tested their Silver Nano Cluster DNA probes with eight different types of genetic material and found that they work outright with six of them. But more importantly, they figured out how to fix the ones that didn’t. This indicates that their method will work in the detection of almost all types of miRNAs, also in all likelihood for cancer related miRNAs. The most widespread current miRNA detection method requires some 48 hours of lab work from raw samples. The new method can do the same job of detection within a maximum of 6 hours. University of Copenhagen

Nearly 23 percent of American women of childbearing age met or exceeded the median blood levels for all three environmental chemical pollutants — lead, mercury, and PCBs — tracked in an analysis of data on thousands of women by Brown University researchers. All but 17.3 percent of the women aged 16 to 49 were at or above the median blood level for one or more of these chemicals, which are passed to foetuses through the placenta and to babies through breast milk.
The study identified several risk factors associated with a higher likelihood of a median-or-higher ‘body burden’ for two or more of these chemicals.
The three pollutants are of greatest interest because they are pervasive and persistent in the environment and can harm foetal and infant brain development, albeit in different ways, said study lead author Dr. Marcella Thompson. But scientists don’t yet know much about whether co-exposure to these three chemicals is more harmful than exposure to each chemical alone. Most researchers study the health effects of exposure to an individual chemical, not two or three together.
‘Our research documents the prevalence of women who are exposed to all three of these chemicals,’ said Thompson, who began the analysis as a doctoral student at the University of Rhode Island College of Nursing and has continued the research as a postdoctoral research associate for Brown University’s Superfund Research Program with co-author Kim Boekelheide, professor of pathology and laboratory medicine. ‘It points out clearly the need to look at health outcomes for multiple environmental chemical co-exposures.’
Most of the childbearing-age women — 55.8 percent — exceeded the median for two or more of the three pollutants.
Data were collected between 1999 and 2004 from 3,173 women aged 16 to 49 who participated in the Centers for Disease Control and Prevention National Health and Nutrition Examination Survey (NHANES). The survey was designed to represent the national population of 134.5 million women of childbearing age. Because the original study also elicited a wide variety of information on health behaviours, socio-economic and demographic characteristics, Thompson and Boekelheide were able to identify specific risk factors associated with increased odds of having higher blood levels of lead, mercury, and PCBs.
They found several statistically significant risk factors. The most prominent among them was age. As women grew older, their risk of exceeding the median blood level in two or more of these pollutants grew exponentially to the point where women aged 30 to 39 had 12 times greater risk and women aged 40 to 49 had a risk 30 times greater than those women aged 16 to 19.
Thompson said women aged 40 to 49 would be at greatest risk not only because these chemicals accumulate in the body over time, but also because these women were born in the 1950s and 1960s before most environmental protection laws were enacted.
Fish and heavy alcohol consumption also raised the risk of having higher blood levels. Women who ate fish more than once a week during the prior 30 days had 4.5 times the risk of exceeding the median in two or more of these pollutants. Women who drank heavily had a milder but still substantially elevated risk.
Fish, especially top predators like swordfish and albacore tuna, are known to accumulate high levels of mercury and PCBs, Thompson said. However, there is no known reason why they found a statistically higher association between heavy drinking and a higher body burden of pollutants.
One risk factor significantly reduced a woman’s risk of having elevated blood levels of the pollutants, but it was not good news: breastfeeding. Women who had breastfed at least one child for at least a month sometime in their lives had about half the risk of exceeding the median blood level for two or more pollutants. In other words, Thompson said, women pass the pollutants that have accumulated in their bodies to their nursing infants.
Although the study did not measure whether women with higher levels of co-exposure or their children suffered ill health effects, Thompson said, the data still suggest that women should learn about their risks of co-exposure to these chemicals well before they become pregnant. A woman who plans to become pregnant in her 30s or 40s, for example, will have a high relative risk of having higher blood levels of lead, PCBs, and mercury.
‘We carry a history of our environmental exposures throughout our lives,’ Thompson said. Brown University