Publisher Health

An international research team has identified metabolic ‘signatures’ in urine that can determine the quality of diets in children across Europe and predict their metabolic health.
Their methods, described today in eLife, could be used in addition to traditional questionnaires to objectively assess dietary patterns in children, and in future studies to evaluate the quality of participants’ diets. This knowledge can provide further insights on shared biological pathways that characterise healthy and unhealthy dietary patterns, as well as diet-related metabolic changes associated with diseases such as diabetes.
While previous research has identified diet-related changes in people, these studies have focused largely on selected food groups including fruit, vegetables, meat and seafood. On the other hand, dietary patterns related to the consumption of ultra-processed foods, which are high in sugars and fat, have been studied much less, despite more of this food being consumed across the globe.
“The objective assessment of dietary habits is important for the prevention of chronic diseases. Public health organisations typically base their recommendations on research on dietary habits,” says Alexandros Siskos, Research Associate at Imperial College London, UK. Siskos is a co-first author of the study alongside Nikos Stratakis (ISGlobal, Barcelona), and Eleni Papadopoulou (Norwegian Institute of Public Health, Oslo, Norway).
“Urinary metabolic profiling is a promising, powerful tool for assessing food intake and can help us understand metabolic alterations in people in response to their diet quality,” adds Nikos Stratakis, who was a Postdoctoral Researcher at Keck School of Medicine of USC, Los Angeles, US, at the time the study was carried out, and is now a Postdoctoral Fellow at ISGlobal. “We set out to develop a way to identify urinary metabolites associated with a Mediterranean diet or the consumption of ultra-processed foods in European children and to determine the extent to which these metabolites might be able to predict disease risk.”
The team’s multi-country study is embedded within the Human Early-Life Exposome (HELIX) project — a collaborative project that includes six population-based birth cohort studies in Europe, from the UK, France, Lithuania, Spain, Norway and Greece. The population for the current study consisted of 1,147 children from the project with available information on dietary intake, C-peptide levels in their blood plasma, and metabolomic biomarkers in their urine collected during a HELIX follow-up at a mean age of almost eight years old.
The researchers applied a technique called nuclear magnetic resonance (NMR) spectroscopy to profile the urinary metabolites from this population. Their work revealed a common panel of four metabolites — hippurate, N-methylnicotinic acid, urea and sucrose — that indicated whether a child followed a Mediterranean diet or consumed more ultra-processed foods. Children who adhered to a Mediterranean diet had higher levels of hippurate, N-methylnicotinic acid and urea, along with lower levels of sucrose, or sugar. On the other hand, those who consumed more ultra-processed foods had lower levels of hippurate, N-methylnicotinic acid and urea, and higher levels of sugar.
The team then studied the extent to which these metabolites were associated with C-peptide, a substance used as an early indicator of metabolic disease risk. For each cohort, the researchers assessed the concentration of C-peptide in the blood plasma samples. They found that higher adherence to a Mediterranean diet was associated with lower C-peptide levels, while the opposite was seen for those who consumed more ultra-processed foods.
The findings of this study come with a few limitations, including around the use of NMR spectroscopy for urinary metabolite profiling. While this technique allowed the team to clearly identify and profile metabolites, it limited the number of metabolites they were able to measure across entire urine samples. “Our work should be supplemented with other complementary metabolomic approaches in future, such as mass spectrometry,” says co-senior author Hector Keun, Professor of Biochemistry at Imperial College London. “This would help to enhance the identification and quantification of urinary metabolites associated with diet quality in children.”
“Further studies examining the association of diet quality and related metabolomic profiles with C-peptide will also be needed to replicate our findings,” adds co-senior author Leda Chatzi, Professor of Population and Public Health Sciences at Keck School of Medicine of USC. “For now, our work provides further evidence to support efforts by public health authorities to recommend increased adherence to a Mediterranean diet. Limiting the consumption of ultra-processed foods in childhood could lower the risk of disease later on.”
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Families with young children who have type 1 diabetes use insulin pumps that require a lot of effort to operate. Scientists from all over Europe, including researchers from Leipzig University Hospital, the only site involved in Germany, have shown for the first time in a clinical trial that automated insulin delivery is safe and effective even at the age of one to seven years. The data was recently published in the journal New England Journal of Medicine.
Managing insulin-dependent diabetes in young children is a major challenge. In Germany, people mostly use insulin pumps for controlling blood glucose levels. In combination with continuous glucose monitoring under the skin, this is called sensor-augmented pump therapy. The parents are responsible for manually dosing the insulin and adjusting the elevated blood glucose. This often requires correction, especially at night. Automated insulin delivery systems are available for older children and adolescents, but not for young children. This age group has the highest day-to-day variability in terms of insulin requirements and cannot respond independently to blood glucose. Prolonged periods of elevated blood glucose levels can have a negative impact on brain development and intelligence quotient.
An automated insulin delivery system developed at the University of Cambridge has now been tested on 74 children aged one to seven years and their families from seven paediatric diabetes centres in the UK, Austria, Luxembourg and Germany. Leipzig University Hospital was the only German site involved in the international consortium. Professor Roman Hovorka from the University of Cambridge has developed an Android app — CamAPS FX — for managing blood glucose levels in young children with type 1 diabetes, which automatically adjusts the insulin dose when combined with an insulin pump and continuous glucose monitoring.
More effective than standard therapy for young children
The approach employs a so-called hybrid closed-loop system, in which the parents still have to deliver insulin at mealtimes, but at all other times the algorithm automatically controls the amount of insulin depending on the child’s glucose levels. According to the study data, the system was safe and more effective than the standard therapy used in this age group. Parents reported finally being able to sleep through the night again without having to react to elevated or low blood sugar levels. During the night, blood glucose levels remained in the target area for more than 80 per cent of the time.
PD Dr. med. Thomas Kapellen, head of this study at the diabetes centre at Leipzig University Hospital’s paediatrics department, examined ten children aged four to seven years. “Nine of them are continuing to use the system after the end of the large-scale study, currently as part of a follow-up observation in real life,” said the paediatric diabetologist.
Two hours per day more than before in the desired blood sugar range
All 74 young children who took part in the study used the sensor-augmented mode — the previous standard therapy — for 16 weeks, and then the automated hybrid closed-loop system for 16 weeks. When using the CamAPS FX app, their blood sugar was in the target range for almost three quarters of the day. In total, this amounted to 125 minutes longer per day than with the previous standard therapy. This meant that the study participants spent less than a quarter of the day, 22.9 per cent, above the blood glucose target range. In contrast, there was no difference in hypoglycaemia between the two groups. The app also reduced the mean blood glucose level. When using the new system, the children’s metabolic control was thus significantly improved and within the desired range.
“The app is CE-certified, but at present is not yet covered by health insurance in Germany. Since it is currently the only CE-certified system in the world for children aged one year and up, I hope that it will be approved very soon and the costs then covered by the health insurance funds in Germany,” said Dr Thomas Kapellen.
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A robot has performed laparoscopic surgery on the soft tissue of a pig without the guiding hand of a human — a significant step in robotics toward fully automated surgery on humans. Designed by a team of Johns Hopkins University researchers, the Smart Tissue Autonomous Robot (STAR) is described today in Science Robotics.
“Our findings show that we can automate one of the most intricate and delicate tasks in surgery: the reconnection of two ends of an intestine. The STAR performed the procedure in four animals and it produced significantly better results than humans performing the same procedure,” said senior author Axel Krieger, an assistant professor of mechanical engineering at Johns Hopkins’ Whiting School of Engineering.
The robot excelled at intestinal anastomosis, a procedure that requires a high level of repetitive motion and precision. Connecting two ends of an intestine is arguably the most challenging step in gastrointestinal surgery, requiring a surgeon to suture with high accuracy and consistency. Even the slightest hand tremor or misplaced stitch can result in a leak that could have catastrophic complications for the patient.
Working with collaborators at the Children’s National Hospital in Washington, D.C. and Jin Kang, a Johns Hopkins professor of electrical and computer engineering, Krieger helped create the robot, a vision-guided system designed specifically to suture soft tissue. Their current iteration advances a 2016 model that repaired a pig’s intestines accurately, but required a large incision to access the intestine and more guidance from humans.
The team equipped the STAR with new features for enhanced autonomy and improved surgical precision, including specialized suturing tools and state-of-the art imaging systems that provide more accurate visualizations of the surgical field.
Soft-tissue surgery is especially hard for robots because of its unpredictability, forcing them to be able to adapt quickly to handle unexpected obstacles, Krieger said. The STAR has a novel control system that can adjust the surgical plan in real time, just as a human surgeon would.
“What makes the STAR special is that it is the first robotic system to plan, adapt, and execute a surgical plan in soft tissue with minimal human intervention,” Krieger said.
A structural-light based three-dimensional endoscope and machine learning-based tracking algorithm developed by Kang and his students guides STAR. “We believe an advanced three-dimensional machine vision system is essential in making intelligent surgical robots smarter and safer,” Kang said.
As the medical field moves towards more laparoscopic approaches for surgeries, it will be important to have an automated robotic system designed for such procedures to assist, Krieger said.
“Robotic anastomosis is one way to ensure that surgical tasks that require high precision and repeatability can be performed with more accuracy and precision in every patient independent of surgeon skill,” Krieger said. “We hypothesize that this will result in a democratized surgical approach to patient care with more predictable and consistent patient outcomes.”
The team from Johns Hopkins also included Hamed Saeidi, Justin D. Opfermann, Michael Kam, Shuwen Wei, and Simon Leonard. Michael H. Hsieh, director of Transitional Urology at Children’s National Hospital, also contributed to the research.
The work was supported by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health under award numbers 1R01EB020610 and R21EB024707.
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Materials provided by Johns Hopkins University. Original written by Catherine Graham. Note: Content may be edited for style and length.

In a new study, published in PLOS ONE, scientists from Queen Mary University of London show that their lab-in-a-backpack approach is as effective as commercially available Covid-19 tests at detecting SARS-CoV-2.
The compact kit is relatively inexpensive to make, costing $51 in total. It could offer an alternative testing solution for resource-poor countries or remote areas with little access to well-equipped testing labs or trained personnel to process samples.
The testing kit is based on a simple, non-invasive Covid-19 LAMP test and uses low-cost hardware, including a centrifuge made from recycled computer hard drives to process samples.
The LAMP test is a widely accepted alternative to the commonly used PCR test, has a similar sensitivity but unlike the PCR test does not require temperature cycling, only a single high temperature to amplify any potential virus RNA. This allows the test to be performed with only minimal equipment and reagents. Because the LAMP test uses saliva samples, it also avoids the need for invasive, uncomfortable nasal swabs. However, the high costs of commercially available LAMP tests, as well as the expensive lab equipment required to run them, means that current commercial approaches aren’t suitable for remote locations, or in-home testing.
Regular testing is a key part of global efforts to manage the Covid-19 pandemic, and it is hoped low-cost testing solutions like this could help improve access to fast and effective Covid-19 testing worldwide.
According to the researchers, next steps will include making the kit instructions even more understandable so that people can use them regardless of their experience or language, as well as validating the kit with real patient samples. So, whilst this approach holds promise, further work is needed before the system can be implemented in real-world environments, Professor Smoukov said.
Professor Stoyan Smoukov, Professor of Chemical Engineering at Queen Mary University of London, said: “We are excited for the potential of this mobile lab to do Covid-19 tests and the possibility to democratise access to inexpensive testing technology. It is made possible by our philosophy of creating low-cost instruments whenever possible from advances in electronics, or existing instruments.
“Reuse is a high value option for energy and materials sustainability, and we are glad that rather than exporting electronics waste to developing countries, we can export ways to empower people and turn waste computer hard drives into a centrifuge. The Covid-19 test is a timely application, but we also believe with this CentriDrive kit people could perform a large array of routine blood and urine tests, providing a centrifuge away from central hospital facilities.”
Emily Lin, lead author of the study, said: “In this study, using the LAMP test method in combination with a low-cost centrifuge, we provided an inexpensive, rapid and accurate method for the detection of COVID-19. It will not only provide a viable and inexpensive test kit for regions such as Africa, where innovative solutions are particularly important during the Covid-19 pandemic. It can also be used in resource-rich areas, for example, in high school classrooms to demonstrate how to test for Covid-19.”
Professor Smoukov added: “Combining open access science with open-source hardware lets everyone in the world to test this for themselves with minimal resources. We are also providing this technology to the innovators and entrepreneurs in the Pan-African Innovation Competition Queen Mary is running to inspire inventors in Africa. Perhaps this royalty-free invention will let people tinker and educate themselves and others on how different blood or virus tests work. Or the simplicity and cost advantage may inspire people to base a company around it.”
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When the COVID-19 pandemic hit, scientists across the U.S. Department of Energy’s (DOE) national laboratory complex turned to the nation’s most powerful supercomputers and other tools to discover molecules that might treat the disease. A study published in the Journal of Chemical Information and Modeling reports the discovery of a molecule with significant potential to disable the virus.
The molecule was identified using high-throughput virtual screening — a search through a library of 6.5 million in-stock compounds that could quickly be scaled up for drug production. The team used computer-based molecular docking studies to identify molecules that could bind to certain targets on the virus’s main protease (Mpro) — an enzyme the virus uses to make copies of itself. They also conducted high-throughput laboratory screening experiments, structural studies, and molecular dynamics simulations to learn how these potential inhibitors and the enzyme interact. The goal was to find molecules that could jam up the enzyme’s function, which would stop the virus from replicating.
The computational team, which included scientists from the Computational Science Initiative (CSI) at DOE’s Brookhaven National Laboratory, identified 72 candidate molecules with potential to inhibit Mpro. Other teams ran laboratory experiments testing those molecules’ ability to inhibit the virus. Structural studies using, for example, x-ray crystallography revealed how the candidate molecules fit together with the virus enzyme. Additional computer-based simulations provided details about how those interactions alter the enzyme.
The paper describes how the most promising candidate, known as MCULE-5948770040, binds with Mpro and changes its shape in a way that inhibits the enzyme’s function. Future experiments will explore whether the molecule can be developed into a new drug for treating COVID-19.
“Scientists from Brookhaven’s CSI played an important role in generating and analyzing large volumes of data that led to scientific insight,” said Shantenu Jha, one of the corresponding authors on the paper, who holds a joint appointment with Brookhaven and Rutgers University. “CSI folks also established the ‘software infrastructure’ to support the large-scale computations,” he said.
Given the urgency of the pandemic, “this was a very high-intensity project with a great level of ‘learning while doing,'” Jha noted.
CSI’s Hubertus Van Dam, another study co-author, agreed, saying he was inspired by “tackling, for me, a new set of problems with a new set of methods in a large team.”
The team for this paper included scientists from five national laboratories and four collaborating universities, all supported by the DOE Office of Science through the National Virtual Biotechnology Laboratory (NVBL). NVBL is a consortium of DOE national laboratories focused on response to COVID-19, with funding provided by the Coronavirus CARES Act.
Kerstin Kleese Van Dam, director of CSI at Brookhaven, served as leader of Brookhaven’s role in the NVBL medical therapeutics project.
“A key weapon in our arsenal in the fight against COVID-19 are medicines to treat those infected,” she said. “The NVBL medical therapeutics project brought to bear the combined might of DOE scientists, and key experimental and computational facilities to discover new COVID treatments.
“This paper describes not only some of our successes, but also gives a glimpse behind the scenes at the scientific ingenuity needed to make those exciting discoveries possible.”
The research was also supported by the DOE-Exascale Computing Project.
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New research has shown that over-activity in a specific area of the brain is linked to certain symptoms of Schizophrenia, opening up possibilities for the development of more targeted treatments.
Researchers from the University of Nottingham found that faulty inhibitory neurotransmission and abnormally increased activity in the hippocampus doesn’t disrupt the ability to filter out irrelevant information, a key process which has been shown to be deficient in patients with schizophrenia and is thought to cause hallucinations or delusions but does disrupt associative learning. Deficits in associative learning, such as Pavlovian fear conditioning, have been linked to the negative symptoms of the disorder which include reduced motivation and disrupted emotional and reward processing. Their findings have been published in eNeuro.
Schizophrenia is a major illness. At any one time about 220,000 people are being treated for schizophrenia in the UK by the NHS. It is psychotic illness which exhibits itself in three ways: negative symptoms such as lethargy, apathy and social withdrawal, positive symptoms such as hallucinations and delusions and cognitive symptoms such as impaired memory. Either or all three may be present in an individual at the same time.
Neurons in the brain interact by sending each other chemical messages, so-called neurotransmitters. Gamma-aminobutyric acid (GABA) is the most common inhibitory neurotransmitter, which is important to restrain neural activity, preventing neurons from getting too trigger-happy and from firing too much or responding to irrelevant stimuli.
The hippocampus is a part of the brain that sits within our temporal lobes and plays a major role in our memories and emotions. This latest research has implications for understanding more about how this part of the brain affects specific aspects of schizophrenia.
The study was carried led by post-doctoral researcher Stuart Williams, he said: “We know that people with schizophrenia have increased hippocampal activity, we wanted to explore this further and find out exactly how this manifests itself. Through our research carried out in rats we were able to ascertain the importance of GABAergic inhibition within the hippocampus in relation to certain symptoms associated with schizophrenia. Specifically, we found no evidence that faulty inhibition within the hippocampus disrupts behaviours related to the underlying cognitive processes which are thought to contribute to the onset of hallucinations or delusions but did find that it may contribute to some of the negative symptoms, disrupting associative learning in the form of conditioned fear.”
This study has important implications for developing treatments for the negative symptoms of schizophrenia.
Stuart continues: “By revealing previously unknown detail about the role of aberrant activity in the hippocampus, we are providing insights into the behavioural consequences that disruption of specific neural structures, such as the hippocampus, have in schizophrenia. This could help to develop more targeted treatments that improve the management of specific aspects of schizophrenia symptomatology such as improving negative symptoms, potentially by dampening down this over-activity in the hippocampus.
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The entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into human cells is an essential step for virus transmission and development of COVID 19. Although the lung epithelial cells are its initial target, SARS-CoV-2 also can infect endothelial cells. Endothelial cells are the major constituents of the vascular system and cardiovascular complication is a hallmark of severe COVID-19. Angiotensin-converting enzyme 2 (ACE2) is the entry receptor for SARS-CoV-2. However, the possible involvement of other cellular components in the viral entry is not fully understood.
A team of researchers from the Boston University School of Medicine (BUSM) has identified extracellular vimentin as an attachment factor that facilitates SARS-CoV-2 entry into human cells. Vimentin is a structural protein that is widely expressed in the cells of mesenchymal origin such as endothelial cells and a potential novel target against SARS-CoV-2, which could block the infection of the SARS-CoV-2.
“Severe endothelial injury, vascular thrombosis, and obstruction of alveolar capillaries (tiny air sacs scattered throughout the lungs) are common features of severe COVID-19. Identification of vimentin as a host attachment factor for SARS-CoV-2 can provide new insight into the mechanism of SARS-CoV-2 infection of the vascular system and can lead to the development of novel treatment strategies,” said corresponding author Nader Rahimi, PhD, associate professor of pathology & laboratory medicine at BUSM.
The researchers used liquid chromatography-tandem mass spectrometry (LC-MS/MS) and identified vimentin as a protein that binds to the SARS-CoV-2 spike (S) protein and facilitates SARS-CoV-2 infection. They also found that depletion of vimentin significantly reduces SARS-CoV-2 infection of human endothelial cells. In contrast, over-expression of vimentin with ACE2 significantly increased the infection rate. “More importantly, we saw that the CR3022 antibody inhibited the binding of vimentin with CoV-2-S-protein, and neutralized SARS-CoV-2 entry into human cells,” explained Rahimi.
Collaborators from BUSM included Elke Mühlberger, PhD, Vipul Chitalia, MD, PhD and Catherine E. Costello, PhD.
These findings appear online in the Proceedings of the National Academy of Sciences.
This research was supported in part through a grant from BUSM Genome Science Institute and ARC-COVID-19 (NR and CEC); NIH grants R24 GM134210 and S10 OD021728 (to CEC), funding from BUSM COVID-19 ARC (to CEC and NR) and BUSM Clinical & Translational Science Institute awards from NIH NCATS grant UL1TR001430 (to EM and CEC). Fast Grants (EM), the Evergrande COVID-19 Response Fund Award from the Massachusetts Consortium on Pathogen Readiness (EM and AGS). NIH R01 AI146779 (AGS) and NIGMS T32 GM007753 (AGS).
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Signs of inflammation in the blood reliably predict and identify severe depression in pregnancy, reports a new study led by scientists at Van Andel Institute and Pine Rest Christian Mental Health Services.
The team’s analysis established a set of 15 biological markers found in the blood that can predict if pregnant women will experience significant depressive symptoms with 83% accuracy. The findings could give physicians a much-needed tool to identify women who may be at risk for depression and better tailor their care throughout pregnancy.
Nearly one in five new mothers experience severe depression during or after pregnancy and an estimated 14% have suicidal thoughts. Inflammation can lead to worsening depressive symptoms, and pregnancy is a major inflammatory event.
“Depression isn’t just something that happens in the brain — its fingerprints are everywhere in the body, including in our blood,” said Lena Brundin, M.D., Ph.D., a VAI professor and co-senior author of the study. “The ability to predict pregnancy-related depression and its severity will be a gamechanger for protecting the health of mothers and their infants. Our findings are an important leap forward toward this goal.”
The study, published today in Translational Psychiatry, is among the first of its kind and followed 114 volunteers from Spectrum Health’s Obstetrics and Gynecology Clinics throughout their pregnancies. Participants provided blood samples and underwent clinical evaluations for depressive symptoms in each trimester and the postpartum period.
“Having an objective and easily accessible method associated with depression risk, such as a blood test, provides a unique tool for helping identify women who may develop depression during pregnancy,” said Eric Achtyes, M.D., M.S., staff psychiatrist at Pine Rest, an associate professor at Michigan State University and co-senior author of the study. “Our findings are an exciting development and an important first step toward using these types of methods more widely to help patients. Our next steps include replicating the results in additional patient samples to verify cut-offs for depression risk.”
Co-authors on the study include Qiong Sha, Ph.D., Zach Madaj, M.S., Sarah Keaton, Ph.D., Martha L. Escobar Galvis, Ph.D., and Stanislaw Krzyzanowski of VAI; LeAnn Smart of Pine Rest; Asgerally T. Fazleabas, Ph.D., and Richard Leach, M.D., of Michigan State University College of Human Medicine; and Teodor T. Postolache, M.D., of University of Maryland School of Medicine.
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The blood-brain barrier keeps foreign substances from entering the brain. That’s good when it comes to toxins and germs, but it makes treating tumors in the brain trickier. By shielding the brain from things that would harm it, the blood-brain barrier also blocks the chemotherapy that would help it.
William Walker — a researcher with the West Virginia University School of Medicine — is investigating whether the blood-brain barrier is more likely to admit chemotherapy drugs at different times of day.
His study — funded by the National Institutes of Health — shows that the blood-brain barrier is dynamic rather than static and suggests that properly timed chemotherapy treatments could better reach the tumors they’re targeting.
“We are not the first ones to show that chrono-chemotherapy is beneficial, but we’re the first to show that it’s beneficial in the treatment of brain metastasis,” said Walker, a postdoctoral fellow in the Department of Neuroscience.
His findings appeared in “Frontiers in Oncology.”
Walker and his colleagues delivered chemotherapy into mice that had breast cancer, which had traveled to the brain.

Researchers exploring dementia-related proteins in the brain identified Apolipoprotein E (ApoE) as a key misfolded protein. About 25% of individuals, and 50% of individuals with Alzheimer disease, have a genetic mutation, the APOE ε4 allele — a known risk factor for the disease. The researchers were surprised to find that even in the brains of patients without the disease-driving APOE ε4 allele, ApoE proteins were strongly enriched in dementia. Their findings appear in The American Journal of Pathology, published by Elsevier.
“Dementia is very complex, but you can simplify it: the disease is caused by ‘gloppy proteins’ in the brain,” explained lead investigator Peter T. Nelson, MD, PhD, Sanders-Brown Center on Aging and Department of Pathology, University of Kentucky, Lexington, KY, USA. “I’m not making light of it — these ‘sticky’ misfolded proteins often end up destroying the brain, the mind, the memories and everything else for millions of people who suffer from dementia. We want to understand specifically which proteins are the problem.”
The investigators used mass spectrometry to characterize the complete set of proteins, or proteome, from the amygdalae of 40 participants from the University of Kentucky Alzheimer’s Disease Center autopsy cohort. The amygdala is vulnerable to mis-aggregated proteins associated with dementia and is often affected even at the earliest stages of disease. The subjects ranged from cognitively normal to severe amnestic dementia. Although previous studies have examined the human amygdala proteome, none have reported on a sample of this size with dementia subjects and control subjects for comparison.
As anticipated, portions of proteins previously associated with neurodegenerative diseases were found in the brains of patients with dementia, including proteins called Tau (associated with neurofibrillary tangles), Aβ (associated with amyloid plaques), and α-Synuclein (associated with Lewy Body disease). Aβ and α-Synuclein correlated strongly with clinical diagnosis of dementia. Tau and Aβ proteins, but not α-Synuclein, were occasionally detectible in cognitively normal subjects and those with mild cognitive impairment. Overall, Dr. Nelson observes, the findings for these proteins were in line with expectations.
The data also revealed a close correlation between dementia diagnosis and the detection of ApoE peptides in the brain. The correlation with dementia for ApoE was even stronger than that seen for Tau, Aβ, or α-Synuclein. Moreover, the ApoE peptides were significantly enriched even in dementia patients who lack the APOE ε4 allele. The results emphasize the relevance of the ApoE protein as an aberrantly aggregated protein in its own right, rather than just an “upstream” genetic risk factor.
“Our study adds to an evolving appreciation of multiple misfolded proteins in the human brain and moves the field forward by emphasizing that ApoE may be a stong contributor to the dementia prototype, even in individuals who do not have the disease-driving version of the APOE gene,” said Dr. Nelson. “Even in persons lacking the APOE ε4 allele, ApoE may indeed be among the most impactful ‘gloppy proteins’ in aging brains.”
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