Newly discovered gene mutations may help explain the cause of a disease that drastically impairs walking and thinking.
Mutations have been found in the bassoon (BSN) gene, which is involved with the central nervous system, in patients with symptoms similar to, but different from, a rare brain disorder called progressive supranuclear palsy (PSP).
PSP, a form of Parkinson’s disease, is often difficult to diagnose because it can affect people in different ways. Serious problems often include difficulty with walking and balance in addition to a decline in cognitive abilities such as frontal lobe dysfunction.
A team of Japanese researchers investigated patients whose symptoms resembled not only PSP but also Alzheimer’s disease. Despite similarities in the symptoms, detailed pathological analyses showed no resemblance to either disease, which prompted the team to further research the new disease’s underlying mechanism.
They first analysed the genomes of a Japanese family with several members displaying PSP-like symptoms. They identified a mutation in the BSN gene only in family members with symptoms. These individuals did not have mutations in the 52 other genes associated with PSP and other neurological disorders such as Alzheimer’s and Parkinson’s. This was the first time BSN gene is associated with a neurological disorder.
The researchers also detected three other mutations in the BSN gene in four out of 41 other patients displaying sporadic, or non-familial, PSP-like symptoms. None of the BSN mutations were detected in a random sample of 100 healthy individuals, underscoring the strong involvement of BSN mutations in the disease.
An autopsy done on one of the family members with the BSN mutation showed an accumulation of a protein called tau in the brain, which is not seen in a normal brain. The researchers believe that the BSN mutation is involved in the tau accumulation, which could cause the development of PSP-like symptoms. An experiment introducing a mutated rat BSN gene to cultured cells also suggested that the mutation causes the accumulation of tau. Communication between nerve fibres could also be affected, as BSN protein play a role in it.
ScienceDailywww.sciencedaily.com/releases/2018/03/180323093731.htm

There is as yet no cure for Alzheimer’s disease. It is often argued that progress in drug research has been hampered by the fact that the disease can only be diagnosed when it is too late for an effective intervention. Alzheimer’s disease is thought to begin long before patients show typical symptoms like memory loss. Scientists have now developed a blood test for Alzheimer’s disease and found that it can detect early indicators of the disease long before the first symptoms appear in patients. The blood test would thus offer an opportunity to identify those at risk and may thereby open the door to new avenues in drug discovery.
One of the hallmarks of Alzheimer’s disease is the accumulation of amyloid-β plaques in the patient’s brain. The blood test, developed by Klaus Gerwert and his team at Ruhr University Bochum, Germany, works by measuring the relative amounts of a pathological and a healthy form of amyloid-β in the blood. The pathological form is a misfolded version of this molecule and known to initiate the formation of toxic plaques in the brain. Toxic amyloid-β molecules start accumulating in the patients’ body 15-20 years before disease onset. In the present study, Gerwert and colleagues from Germany and Sweden addressed whether the blood test would be able to pick up indications of pathological amyloid-β in very early phases of the disease.
The researchers first focused on patients in the early, so called prodromal stages of the disease from the Swedish BioFINDER cohort conducted by Oskar Hanson. They found that the test reliably detected amyloid-β alterations in the blood of participants with mild cognitive impairment that also showed abnormal amyloid deposits in brain scans.
In a next step, Gerwert and colleagues investigated if their assay was able to detect blood changes well ahead of disease onset. They used data from the ESTHER cohort study, which Hermann Brenner started in 2000 at DKFZ, comparing blood samples of 65 participants that were later in the follow-up studies diagnosed with Alzheimer’s disease with 809 controls. The assay was able to detect signs of the disease on average eight years before diagnosis in individuals without clinical symptoms. It correctly identified those with the disease in almost 70% of the cases, while about 9% of true negative subjects would wrongly be detected as positive. The overall diagnostic accuracy was 86%.
Currently available diagnostic tools for Alzheimer’s disease either involve expensive positron emission tomography (PET) brain scans, or analyse samples of cerebrospinal fluid that are extracted via lumbar puncture. The researchers suggest that their blood test serves as a cheap and simple option to pre-select individuals from the general population for further testing by these more invasive and costly methods to exclude the falsely positive subjects.
EMBOwww.embo.org/news/press-releases/2018/a-new-blood-test-useful-to-detect-people-at-risk-of-developing-alzheimer-s-disease

Van Andel Research Institute (VARI) announced that the work of its scientists is featured in 27 papers focused on the output of The Cancer Genome Atlas (TCGA).
The findings are the result of a global scientific collaboration and mark the culmination of TCGA, a multi-institutional, joint effort between the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI) to develop a comprehensive scientific resource for better categorizing cancer. The more than decade-long initiative is the most in-depth undertaking of its kind, spanning 10,000 tumours across 33 cancer types.
“TCGA’s findings have greatly deepened our molecular understanding of the major cancer types,” said Peter W. Laird, Ph.D., a professor at VARI who led the DNA methylation analysis for TCGA Research Network and who is senior author on two of today’s papers. “It is our hope that these publications will serve as a guide for scientists who plan to harness TCGA’s robust data to develop new, more personalized methods of patient care.”
This research, which represents the project’s capstone, joins dozens of other papers that have been published since TCGA’s inception in 2005. Collectively, they provide a highly detailed description of molecular changes occurring in all major human cancers. The use of this molecular atlas is rapidly expanding, with more than 1,000 publications citing TCGA data in 2017 alone.
TCGA data may be accessed through the National Cancer Institute’s Genomic Data Commons Data Portal (portal.gdc.cancer.gov).
Along with Laird, VARI Assistant Professor Hui Shen, Ph.D., contributed to many of today’s papers, summaries of which may be found below. Shen also is one of six experts who authored retrospectives on TCGA’s legacy, which also were published.
A full list of papers may be found at www.cell.com/consortium/pancanceratlas.
Van Andel Institutewww.vai.org/news-release-4-5-2018/

A new research-based point-of-care test has been developed in Finland for detecting the Lyme neuroborreliosis spread by ticks. The test makes rapid initiation of antibiotic treatment possible for patients with borreliosis, which reduces the post-treatment symptoms related to the disease. At the same time, unnecessary antibiotic treatments can be avoided.
The diagnosis of Lyme neuroborreliosis, a tick-borne infection of the nervous system, relies on infection symptoms, cerebrospinal fluid tests, and detection of the antibody production by the activated immune response.
A Finnish company, Reagena, has developed a new point-of-care test to accompany these methods. The test speeds up the diagnostics and helps to target antibiotic treatment appropriately. The idea for the test was developed by Assistant Professor in Bacteriology, Specialist in Clinical Microbiology Jukka Hytönen from the University of Turku whose research group also validated the test.
The new point-of-care test measures CXCL13 concentration in cerebrospinal fluid, since a high CXCL13 concentration is almost exclusively related to untreated neuroborreliosis. Therefore, the CXCL13 chemokine concentration in the cerebrospinal fluid is a new, important biomarker in the diagnostics of neuroborreliosis. The CXCL13 concentration increases more rapidly in early neuroborreliosis than the antibody concentration in the cerebrospinal fluid, and on the other hand, it declines rapidly after the initiation of antibiotic treatment.
– We have demonstrated that this point-of-care test is extremely efficient. As a result, we suggest that the diagnostic practice for neuroborreliosis in Finland would be reorganised so that the CXCL13 concentration would be measured immediately after the lumbar puncture for cerebrospinal fluid. In the current practice, the concentration results may take up to a week, whereas the new point-of-care test provides quick results, says Hytönen.
With the new test, antibiotic treatment can be targeted to those patients with a high probability of neuroborreliosis. According to Hytönen, it is important to note that a rapidly initiated treatment reduces the post-treatment symptoms related to neuroborreliosis. At the same time, unnecessary treatment initiated just in case can be avoided, which is essential in order to minimise the negative effects related to antibiotics and to prevent the development of antibiotic resistance of bacteria.
Doctors Often Initiate Antibiotic Treatments without Laboratory Results
The clinical pictures of borreliosis vary from local skin infection to infections of the central nervous system, joints or the heart. A typical red rash, the so called erythema migrans lesion, developing and spreading around the tick bite should always be treated with antibiotics without laboratory tests.
– If the rash does not develop or is not diagnosed in the early stages of borreliosis, for example due to its location, the infection may spread to other organs from the skin. Symptoms of the disseminated disease include various neurological symptoms, such as facial nerve paralysis and different types of pain in the limbs and body, notes Hytönen.
The diagnosis of Lyme neuroborreliosis is always clinical-based, meaning it is based on the symptoms experienced by the patient and the doctor’s findings, but laboratory tests are necessary to support the diagnostics. At the moment, the most important laboratory test in the diagnostics of neuroborreliosis is the assay of Borrelia-specific antibodies from the patient’s blood and cerebrospinal fluid.
University of Torkuwww.utu.fi/en/news/news/Pages/New-Point-of-care-Test-Quickly-Detects-Lyme-Neuroborreliosis.aspx

ELITechGroup, a leading company in sample-to-result molecular diagnostics, and R-Biopharm, a globally active life science company, have announced a worldwide agreement to strengthen their positions in molecular infectious disease testing. Under this agreement, R-Biopharm and ELITechGroup will cooperate in the development, production and marketing of Real-Time PCR reagents.
“We are very pleased to have won R-Biopharm as a partner to expand our molecular diagnostics portfolio.” said Christoph Gauer, CEO of ELITechGroup. “This collaboration will contribute to complete the menu of our sample-to-result system ELITe InGenius^®. We will increase the overall number of CE-IVD assays from currently 23 to 33 by the end of 2018 making ELITe InGenius® the system with the broadest CE-IVD menu on the market.”
“Collaborating with ELITechGroup will leverage and strengthen the position of R-Biopharm in the field of Molecular Diagnostics, stated Ralf Dreher, CEO of R-Biopharm. As Molecular Diagnostics is one key pillar within the cross divisional strategy in the R-Biopharm Group, we are confident that this partnership will contribute significantly towards the overall success of the company.”
www.elitechgroup.comwww.r-biopharm.de