New retinal biomarker for identifying early Alzheimer’s disease

Researchers at the Complutense University of Madrid (UCM) have identified changes in retinal layer thickness, inflammation or thinning in patients with mild Alzheimer’s disease. These changes are identified with non invasive assessment using optical coherence tomography may be an important biomarker for early diagnosis.

Researchers observed that in some patients diagnosed with Alzheimer’s disease, the retinal layers presented neurodegeneration, whereas in others they presented neuroinflammation, the stage prior to neurodegeneration, a finding which can be used to diagnose the disease before other tests.

The study was conducted with a group of 19 patients selected from 2124 clinical histories at the San Carlos Hospital Clinic Geriatric Service in Madrid. These patients had very early stage Alzheimer’s disease and did not present any other disease that affected the retina. The study also included a control group comprising 24 volunteers similar in age and other characteristics but without any relevant disease. The results of this investigation has been published in Scientific Reports.

New biomarkers to predict the success of diabetic macular edema treatment

Researchers have found new biomarkers that predict prognosis following current treatments for diabetic macular edema. The research was led by Dr. Rajeev Muni, a vitreoretinal surgeon at St. Michael’s Hospital. The study is published in the journal JAMA Ophthalmology.

Diabetic macular edema is one the common complication of Diabetes. It is associated with the accumulation of fluid in the macula, an area in the center of the retina responsible for sharp vision. The fluid buildup causes the macula to swell and thicken, which causes vision problems. Dr. Muni said diabetic macular edema is the leading cause of vision loss in people under the age of 65 in North America.

Treatment for diabetic macular edema requires a sometimes painful injection in the eye, in some cases as often as once a month. Dr. Rajeev Muni said that while this treatment has been a “game-changer,” preserving and even restoring vision in people who might otherwise have gone blind, some people respond to it better than others.

In this study, researchers took fluid samples from the anterior, chamber of the eyes from 48 patients who were then treated with a ranibizumab injection. They found that low levels of vascular endothelial growth factor (VEGF) and high levels of intercellular adhesion molecule 1 (ICAM-1) are associated with the good response following ranibizumab injection.

“Now we have a novel biomarker to determine who will respond best to treatment,” said Dr. Rajeev Muni. “The prospect of ongoing injections in the eye is daunting for patients. The fact that we can now measure a protein in the eye that allows us to predict which patients are less likely respond to treatment could lead to more personalized and tailored medicine and fewer injections. This could alleviate the treatment burden on patients and the health-care system.”

Citation: Hillier, Roxane J., Elvis Ojaimi, David T. Wong, Michael Y. K. Mak, Alan R. Berger, Radha P. Kohly, Peter J. Kertes, Farzin Forooghian, Shelley R. Boyd, Kenneth Eng, Filiberto Altomare, Louis R. Giavedoni, Rosane Nisenbaum, and Rajeev H. Muni. “Aqueous Humor Cytokine Levels and Anatomic Response to Intravitreal Ranibizumab in Diabetic Macular Edema.” JAMA Ophthalmology, 2018. doi:10.1001/jamaophthalmol.2018.0179.

Research funding: Novartis Pharmaceuticals Canada Inc., Retina Foundation of Canada.

Adapted from press release by St. Michael’s Hospital.

New biomarkers for assessing Alzheimers dementia risk and early diagnosis

Researchers from the University of Texas have analyzed biomarkers to predict future risk of dementia. Their findings are published in journal Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association. 

Dementia is a rising tidal wave of devastation for families and society. Age is the biggest risk factor. Alzheimer’s disease, which is the leading cause of dementia, is the sixth-leading cause of death in the United States, and more than 5 million Americans are currently living with Alzheimer’s. That figure is expected to triple by 2050.

Researchers analyzed metabolites in blood samples taken from 22,623 individuals, including 995 who went on to develop dementia. The participants were enrolled in eight research cohorts in five countries. They found that higher blood concentrations of branched-chain amino acids were associated with lower risk of future dementia. Another molecule, creatinine, and two very low-density lipoprotein (VLDL)specific lipoprotein lipid subclasses also were associated with lower risk of dementia. On the other hand, one high-density lipoprotein (HDL) and one VLDL lipoprotein subclass were associated with increased dementia risk.

These findings will broaden the search for drug targets in dementia caused by Alzheimer’s disease, vascular disease, and other subtypes, said Dr. Seshadri, professor of neurology at UT Health San Antonio. “It is now recognized that we need to look beyond the traditionally studied amyloid and tau pathways and understand the entire spectrum of pathology involved in persons who present with symptoms of Alzheimer’s disease and other dementias,” Dr. Seshadri said. “It is exciting to find new biomarkers that can help us identify persons who are at the highest risk of dementia.”

The study was in persons of European ancestry and was carried out in collaboration with researchers in Finland, the Netherlands, the United Kingdom and Estonia. Dr. Seshadri is eager to replicate it in South Texas. “The Glenn Biggs Institute at UT Health San Antonio will expand these studies to include the diverse racial and ethnic groups who live in South Texas,” she said.

Researchers feel that more studies are needed to clarify whether the branched-chain amino acids and other molecules play a causal role in the dementia disease process or are merely early markers of the disease.

Citation: Tynkkynen, Juho, Vincent Chouraki, Sven J. Van Der Lee, Jussi Hernesniemi, Qiong Yang, Shuo Li, Alexa Beiser, Martin G. Larson, Katri Sääksjärvi, Martin J. Shipley, Archana Singh-Manoux, Robert E. Gerszten, Thomas J. Wang, Aki S. Havulinna, Peter Würtz, Krista Fischer, Ayse Demirkan, M. Arfan Ikram, Najaf Amin, Terho Lehtimäki, Mika Kähönen, Markus Perola, Andres Metspalu, Antti J. Kangas, Pasi Soininen, Mika Ala-Korpela, Ramachandran S. Vasan, Mika Kivimäki, Cornelia M. Van Duijn, Sudha Seshadri, and Veikko Salomaa. “Association of branched-chain amino acids and other circulating metabolites with risk of incident dementia and Alzheimers disease: A prospective study in eight cohorts.” Alzheimers & Dementia, 2018. doi:10.1016/j.jalz.2018.01.003.

Adapted from press release by the University of Texas Health Science Center at San Antonio.

Developing new biomarkers for liver cancer with RNA splicing techniques

Researchers at Cold Spring Harbor Laboratory (CSHL), led by Professor Adrian Krainer, have developed a method for identifying splicing-based biomarkers for hepatocellular carcinoma (HCC). They have published their findings in journal Genome Research.

Different versions, or isoforms, of messenger RNAs generated by the human AFMID gene, are represented, showing their relative prevalence in cancerous (top) and non-cancerous tissue (bottom), sampled from throughout the body. Black peaks, representing the normal variant found in adult cells, are much lower in cancerous tissue than in normal tissue. The reverse is true of variants color-coded orange and red, which serve as biomarkers in liver cancer. Credit: Krainer Lab, CSHL

“This study underscores the potential for learning how RNA splicing variants can contribute to cancer and points to these variants as potential biomarkers for cancer progression,” Krainer says.

Splicing refers to a process in which an RNA message copied from information encoded in a gene is edited before it can serve as a blueprint for the manufacture of a specific protein. A gene can give rise to multiple RNA messages, each resulting in a different protein variant, or “isoform.” Variation and errors in RNA splicing cause the production of nonfunctional proteins or proteins with aberrant function, and it is associated with many diseases.

Recent studies have identified splicing irregularities in liver cancer cells. Led by Cold Spring Harbor Laboratory postdoctoral researcher Kuan-Ting Lin, Krainer’s team developed a method that comprehensively analyzes all RNA messages made from a given gene. The team tested their splicing-variant detection method in HCC, by examining RNA messages in hepatocellular carcinoma cells sampled from hundreds of patients.

Researchers found that specific splicing isoforms of gene AFMID is associated poor survival.  These variant isoforms lead cells to manufacture truncated versions of the AFMID protein. These unusual versions of the protein are associated with adult liver cancer cells with mutations in tumor-suppressor genes called TP53 and ARID1A.

Researchers hypothesize that these mutations are associated with low levels of a molecule called NAD+ that is involved in repairing damaged DNA. Restoring missing portions, called exons, to AFMID’s usual RNA message, they propose, might raise NAD+ to normal levels, avoiding mutations in TP53 and ARID1A. The team hopes to use small molecules called antisense oligonucleotides (ASOs) that can bind to RNA, to change the way AFMID’s RNA messages are spliced. Krainer’s team previously used this technique to correct errors in the splicing of the gene SMN2 as a way to treat spinal muscular atrophy (SMA).

Citation: Lin, Kuan-Ting, Wai Kit Ma, Juergen Scharner, Yun-Ru Liu, and Adrian R. Krainer. “A human-specific switch of alternatively splicedAFMIDisoforms contributes toTP53mutations and tumor recurrence in hepatocellular carcinoma.” Genome Research 28, no. 3 (2018): 275-84. doi:10.1101/gr.227181.117.

Research funding: National Institutes of Health

Adapted from press release by Cold Spring Harbor Laboratory (CSHL).

New target receptor for treating depression GPR158

Researchers from the Scripps Research Institute find a new target receptor called GPR158 for treating depression. Their research shows that individuals with high levels of above receptor may be more susceptible to depression following chronic stress.

“The next step in this process is to come up with a drug that can target this receptor,” says Kirill Martemyanov, Ph.D., co-chair of the TSRI Department of Neuroscience and senior author of the new study, which is published in the journal eLife.

“We need to know what is happening in the brain so that we can develop more efficient therapies,” says Cesare Orlandi, Ph.D., the senior research associate at TSRI and co-first author of the study.

The researchers found elevated GPR158 protein in depressed patients, suspected it could play a major role in the disease process. They then conducted an animal study using male and female mice with and without above receptor. Subsequent behavioral tests showed that mice with elevated levels of GPR158 showed signs of depression following chronic stress and suppressing GPR158 protected them from developing depressive behavior and also resilient to stress.

Next, the researchers examined why GPR158 has these effects on depression. The team demonstrated that GPR158 affects key signaling pathways involved in mood regulation in the region of the brain called prefrontal cortex, though the researchers emphasized that the exact mechanisms remain to be established.

Martemyanov explains that GPR158 is a so-called “orphan receptor” (which gets its name because its binding partner/partners are unknown) with a poorly understood biology and mechanism of action. GPR158 appears to work downstream from other important brain systems, such as the GABA, a major player in the brain’s inhibitory control and adrenergic system involved in stress effects.

Laurie Sutton, Ph.D., a research associate at TSRI and co-first author of the study, says this finding matches what doctors have noticed in people who have experienced chronic stress. “There’s always a small population that is resilient they don’t show the depressive phenotype,” says Sutton.

As the search goes on for additional targets for depression, Martemyanov says scientists are increasingly using new tools in genome analysis to identify orphan receptors like GPR158. “Those are the untapped biology of our genomes, with significant potential for development of innovative therapeutics,” he says.

Citation: Sutton, Laurie P., Cesare Orlandi, Chenghui Song, Won Chan Oh, Brian S. Muntean, Keqiang Xie, Alice Filippini, Xiangyang Xie, Rachel Satterfield, Jazmine D W Yaeger, Kenneth J. Renner, Samuel M. Young, Baoji Xu, Hyungbae Kwon, and Kirill A. Martemyanov. “Orphan receptor GPR158 controls stress-induced depression.” ELife 7 (2018). doi:10.7554/elife.33273.

Research funding: National Institutes of Health, University of Iowa, Max Planck Society, Canadian Institutes of Health Research Fellowship.

Adapted from press release by the Scripps Research Institute.

New biomarkers proposed for earlier diagnosis of autism

Researchers at the University of Warwick have developed new blood and urine tests to indicate those with autism. The biomarkers in blood and urine could lead to earlier detection of autism spectrum disorders (ASD) and consequently children with autism could be given appropriate treatment much earlier in their lives. The findings are published in Molecular Autism.

The team was led by Dr Naila Rabbani, Reader of Experimental Systems Biology at the University of Warwick who said: Our discovery could lead to earlier diagnosis and intervention.We hope the tests will also reveal new causative factors. With further testing we may reveal specific plasma and urinary profiles or “fingerprints” of compounds with damaging modifications. This may help us improve the diagnosis of autism spectrum disorders  and point the way to new causes of autism spectrum disorders .”

The team  found a link between autism spectrum disorder and damage to proteins in blood plasma by oxidation and glycation processes where reactive oxygen species (ROS) and sugar molecules spontaneously modify proteins. These advanced glycation end products and and oxidation marker dityrosine were found higher in children with autism spectrum disorder. The team’s research also confirmed the previously held belief that mutations of amino acid transporters are a genetic variant associated with autism spectrum disorder.

The Warwick team worked with collaborators at the University of Bologna, Italy, who recruited locally 38 children who were diagnosed as having with autism spectrum disorder (29 boys and nine girls) and a control group of 31 healthy children (23 boys and eight girls) between the ages of five and 12. Blood and urine samples were taken from the children for analysis.

The Warwick team discovered that there were chemical differences between the two groups. Working with a further collaborator at the University of Birmingham, the changes in multiple compounds were combined together using artificial intelligence algorithms techniques to develop a mathematical equation or “algorithm” to distinguish between autism spectrum disorder and healthy controls. The outcome was a diagnostic test better than any method currently available.

The next steps are to repeat the study with further groups of children to confirm the good diagnostic performance and to assess if these biomarker tests can identify autism spectrum disorder at very early stages, indicate how the autism spectrum disorder is likely to develop further to more severe disease and assess if treatments are working.

Citation: Anwar, Attia, Provvidenza Maria Abruzzo, Sabah Pasha, Kashif Rajpoot, Alessandra Bolotta, Alessandro Ghezzo, Marina Marini, Annio Posar, Paola Visconti, Paul J. Thornalley, and Naila Rabbani. “Advanced glycation endproducts, dityrosine and arginine transporter dysfunction in autism – a source of biomarkers for clinical diagnosis.” Molecular Autism 9, no. 1 (2018). doi:10.1186/s13229-017-0183-3.

Research funding: Naila Rabbani – Warwick Impact Fund, Marina Marini – Fondazione del Monte di Bologna e Ravenna, Fondazione Nando Peretti.

Adapted from press release by the University of Warwick.

New imaging based biomarker to predict success of atrial fibrillation treatment

Researchers report successful use of biomarker based on heart imaging to predict the usefulness of catheter ablation to treat atrial fibrillation (Afib). Researchers analyzed the level of dys-synchrony in the left atrium as useful biomarker for success of the catheter ablation. The study is published in the Journal of the American College of Cardiology: Cardiovascular Imaging.

Atrial fibrillation, diagnosed in 3.4 million Americans and the most common heart rhythm condition in the United States, is marked by irregular and sometimes extremely rapid heart rates that cause fatigue and shortness of breath, and significantly increase the risk of heart failure and stroke. Treatments include drugs to regulate the electrical pulses in the upper chambers of the heart and  increasingly catheter ablation. The procedure involves general anesthesia and imaging guided use of a wire catheter threaded through a vein to the heart to make scores of tiny burns of tissue in which the irregular heartbeats arise. Though catheter ablation procedure is effective in reducing symptoms, there is an estimated 20 to 30 percent failure rate, and cardiologists have long sought various biological or anatomical factors to help them determine in advance which patients are the best candidates for ablation.

“In our study, we found that the best indicator of success is how in sync the left atrium chamber of the heart is when it relaxes,” says Luisa Ciuffo, M.D., a postdoctoral fellow in the Division of Cardiology at the Johns Hopkins University School of Medicine. “Diseased, damaged hearts with a lot of scar tissue don’t contract and relax at the same time throughout the atrium because it is more difficult to rhythmically contract the thicker, tougher damaged tissue.” The analysis to determine the level of dys-synchrony in the left atrium

For the study, designed to identify the best predictors, the researchers used data from 208 atrial fibrillation patients admitted to The Johns Hopkins Hospital. Some 29 percent of the patients were women and the average age of all patients was 59. Prior to the ablation, each subject underwent computed tomography scans or MRIs of their hearts and were followed for an average of 20 months to assess recurrence of Atrial fibrillation or Afib, including a faster than normal heartbeat or an irregular heartbeat lasting longer than 30 seconds. Atrial fibrillation recurred in 101 patients.

The researchers then analyzed various characteristics of the imaging scans from 208 people in a subgroup: 107 of the people with successful ablations compared to 101 of those with failed ablations. Overall, the Johns Hopkins researchers found that patients with recurrent atrial fibrillation had on average more preoperative dys-synchrony throughout the left atrium than those who had successful ablations (3.9 percent versus 2.2 percent), with the higher value indicating more diseased atrium. In a second part of the study researchers wanted to study level of dys-synchrony that would predict success of treatment. They used cut off value of 2.86 percent and found that this model had 76% sensitivity and 81% specificity.

The researchers caution that a more randomized and controlled clinical trial is needed before doctors can reliably use their cardiac imaging analysis routinely with patients, but if confirmed, they say the method should reduce ablation procedures unlikely to work, along with the procedures’ substantial costs and complication risks.

“We believe we are developing a tool that can help with personalized decision-making to help refine patient selection and thus reduce the failure rate by saving candidates with low potential benefit from futile procedures and complications,” says senior author Hiroshi Ashikaga, M.D., Ph.D., assistant professor of medicine at the Johns Hopkins University School of Medicine. Although the risk of complication is small, about 6 percent with ablation, there is still the chance of puncturing the heart or forming a fistula.

Citation: Ciuffo, Luisa, Susumu Tao, Esra Gucuk Ipek, Tarek Zghaib, Muhammad Balouch, Joao A.c. Lima, Saman Nazarian, David D. Spragg, Joseph E. Marine, Ronald D. Berger, Hugh Calkins, and Hiroshi Ashikaga. “Intra-Atrial Dyssynchrony During Sinus Rhythm Predicts Recurrence After the First Catheter Ablation for Atrial Fibrillation.” JACC: Cardiovascular Imaging, 2018. doi:10.1016/j.jcmg.2017.11.028.

Funding: NIH/National Heart, Lung, Blood Institute, W.W. Smith Charitable Trust, Magic That Matters Fund for Cardiovascular Research, Zegar Family Foundation, Edward St. John Foundation, Roz and Marvin H Weiner Family Foundation.

Adapted from press release by John Hopkins Medicine.

Researchers identify biomarker for autism caused by Dup15q syndrome

Researchers at the UCLA Center for Autism Research and Treatment have identified a signature brain-wave pattern for children with autism spectrum disorder related to a genetic condition known as Dup15q syndrome. The research team noted that this signature is among the first quantitative biomarkers identified in electroencephalogram tests discovered for any syndrome highly associated with autism spectrum disorder. Dup15q syndrome a duplication of chromosome 15q11.2-q13.1 is among the most common genetic variants associated with autism disorders. The study was published in PLOS One.

In a two-stage study, the UCLA team first acquired EEG recordings from 11 children with Dup15q syndrome, along with 10 age- and IQ-matched children with autism spectrum disorder but without the Dup15q syndrome, and nine age-matched children developing in typical fashion. EEGs were quantified and statistically analyzed to determine whether beta oscillations, a characteristic EEG signature, in children with Dup15q distinguished them from the two comparison groups. The UCLA team then collected EEG data from a larger group of children at a meeting of the Dup15q Alliance, a national support and research group that the researchers worked closely with on the project.

For children with autism spectrum disorder related to Dup15q, the findings provide a potentially valuable tool for early and accurate diagnosis, development of new drugs, selection of participants for drug trials, and measurement of whether treatments are making the desired impact. There is currently no drug for curing or treating the core symptoms of autism.

Although Dup15q syndrome affects a small proportion of people with the autism spectrum, the identification of a brain-based biomarker could also serve as a bellwether for findings associated with other genetic syndromes related to autism spectrum disorder.

Citation: Frohlich, Joel, Damla Senturk, Vidya Saravanapandian, Peyman Golshani, Lawrence T. Reiter, Raman Sankar, Ronald L. Thibert, Charlotte DiStefano, Scott Huberty, Edwin H. Cook and  Shafali S. Jeste “A Quantitative Electrophysiological Biomarker of Duplication 15q11. 2-q13. 1 Syndrome.” PLoS One 11, no. 12 (2016): e0167179.
DOI: 10.1371/journal.pone.0167179
Research funding: Dup15q Alliance Clinical Research Award and UCLA Intellectual and Developmental Disabilities Research Center.
Adapted from press release by UCLA.

Using ribosomal protein expression patterns as cancer biomarker

A research team at the University of Basel’s Biozentrum has investigated the expression of ribosomal proteins in a wide range of human tissues including tumors and discovered a cancer type specific signature. The study is reported in journal Genome Biology. Researchers think that these signature could be used for predicting progression and survival.

Gene expression level of individual ribosomal proteins (RP) in different types of cancer (blue: lower level; red: higher level compared to normal tissue). Credit: Mihaela Zavolan and Joao Guimaraes, University of Basel, Biozentrum

Prof. Mihaela Zavolan’s research group at the Biozentrum of the University of Basel has now discovered that about a quarter of the ribosomal proteins have tissue-specific expression and that different cancer types have their own individual expression pattern of ribosomal proteins. In the future, these patterns may serve as a prognostic marker for cancer and may point towards new therapeutic opportunities.

Mihaela Zavolan and her co-worker Joao Guimaraes have systematically analyzed ribosomal protein expression in thirty tissue types, three hundred different cell types and sixteen different types of tumors, such as lung and breast cancer. In contrast to previous assumptions, they found a wide variability in ribosomal protein gene expression. In particular, hematopoietic and tumor cells display the most complex expression pattern.

“For us, it was really impressive to see that consistent signatures emerged for the different cancer types after the analysis of distinct data sets including patient samples,” explains first author Guimaraes. “The pattern of the dysregulated proteins is very striking, whereby the expression of some ribosomal proteins is systematically reduced, and of others increased in cancer cells. This suggests that individual ribosomal proteins can either suppress or promote tumorogenesis.”

Furthermore, the scientists discovered a strong relationship between the “signature” in breast cancer and the relapse-free survival. “We were quite surprised to find that the expression level of just three ribosomal proteins allows a fairly accurate prognosis of disease progression, comparable to the best predictive markers that are currently known”, Zavolan points out.

“Our study demonstrates the potential of such expression signatures for the prognosis and perhaps a diagnosis of cancer. We are especially interested in studying the functions of individual ribosomal proteins and hopefully opening the door for new therapeutic options,” explains the scientist.
Citation: Guimaraes, Joao C., and Mihaela Zavolan. “Patterns of ribosomal protein expression specify normal and malignant human cells.” Genome Biology 2016 17:236.
DOI: 10.1186/s13059-016-1104-z
Adapted from press release by University of Basel.

Tau protein as biomarker for predicting recovery time after concussion

Elevated levels of the brain protein tau following a sport-related concussion are associated with a longer recovery period and delayed return to play for athletes, according to a study published in Journal Neurology. The findings suggest that tau, which can be measured in the blood, may serve as a marker to help physicians determine an athlete’s readiness to return to the game.

Brain. Credit: Ashton University.

A team led by Jessica Gill, R.N., Ph.D. of the National Institute of Nursing Research at the National Institutes of Health and Jeffrey Bazarian, M.D., M.P.H. of the University of Rochester Medical Center evaluated changes in tau in 46 Division I and III college athletes who experienced a concussion. Tau, which plays a role in the development of chronic traumatic encephalopathy or CTE, frontotemporal dementia and Alzheimer’s disease was measured in preseason blood samples and again within 6 hours following concussion using an ultra-sensitive technology that allows researchers to detect single protein molecules.

The athletes – a mix of soccer, football, basketball, hockey and lacrosse players from the University of Rochester and Rochester Institute of Technology – were divided into two groups based on recovery time. Athletes in the “long return to play” group took more than 10 days to recover following concussion, while athletes in the “short return to play” group took less than 10 days to return to their sport.

Individuals in the long return to play group had higher levels of tau in their blood 6 hours after concussion compared to those in the short return to play group. Long return to play athletes also exhibited a jump in tau from preseason levels compared to their short return to play counterparts. Statistical analyses showed that higher blood tau concentrations 6 hours post-concussion consistently predicted that an athlete would take more than 10 days to resume play.

The study included both male and female athletes and showed that tau-related changes occurred in both genders across a variety of sports. The team found significant differences based on sex: women made up 61 percent of the long return to play group, but only 28 percent of the short return to play group. Bazarian says this isn’t surprising; it’s well established that females take longer to recover following concussion than males.

Bazarian and Gill acknowledge that the study is limited by its small size and that more research is needed to establish tau as a biomarker of concussion severity. Next steps include getting blood samples from athletes immediately following a concussion to see if the relationship between tau and return to play holds true on the sideline in the first few minutes following a head hit.

Citation: Gill,Jessica,  Kian Merchant-Borna, Andreas Jeromin,  Whitney Livingston, and Jeffrey Bazarian. Acute plasma tau relates to prolonged return to play after concussion. Neurology 2017. DOI: 10.1212/WNL.0000000000003587
Research funding: NIH/Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH/National Institute of Nursing Research.
Adapted from press release by The University of Rochester Medical Center.