Early Alzheimer’s Detection up to 17 Years in Advance

A sensor identifies misfolded protein biomarkers in the blood. This offers a chance to detect Alzheimer’s disease before any symptoms occur. Researchers intend to bring it to market maturity. The dementia disorder Alzheimer’s disease has a symptom-free course of 15 to 20 years before the first clinical symptoms emerge. Using an immuno-infrared sensor developed in Bochum (Germany), a research team is able to identify signs of Alzheimer’s disease in the blood up to 17 years before the first clinical symptoms appear. The sensor detects the misfolding of the protein biomarker amyloid-beta. As the disease progresses, this misfolding causes characteristic deposits in the brain, so-called plaques.

Our goal is to determine the risk of developing Alzheimer’s dementia at a later stage with a simple blood test even before the toxic plaques can form in the brain, in order to ensure that a therapy can be initiated in time,” says Professor Klaus Gerwert, founding director of the Centre for Protein Diagnostics (PRODI) at Ruhr-Universität Bochum (RUB). His team cooperated for the study with a group at the German Cancer Research Centre in Heidelberg (DKFZ) headed by Professor Hermann Brenner.

The team published the results obtained with the immuno-infrared sensor in the journal “Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association” on 19 July 2022. This study is supported by a comparative study published in the same journal on 2 March 2022, in which the researchers used complementary single-molecule array (SIMOA) technology.

The researchers analysed blood plasma from participants in the ESTHER study conducted in Saarland for potential Alzheimer’s biomarkers. The blood samples had been taken between 2000 and 2002 and then frozen. At that time, the test participants were between 50 and 75 years old and hadn’t yet been diagnosed with Alzheimer’s disease. For the current study, 68 participants were selected who had been diagnosed with Alzheimer’s disease during the 17-year follow-up and compared with 240 control subjects without such a diagnosis. The team headed by Klaus Gerwert and Hermann Brenner aimed to find out whether signs of Alzheimer’s disease could already be found in the blood samples at the beginning of the study.

The immuno-infrared sensor was able to identify the 68 test subjects who later developed Alzheimer’s disease with a high degree of test accuracy (0,78 AUC, Area under Curve). For comparison, the researchers examined other biomarkers with the complementary, highly sensitive SIMOA technology – specifically the P-tau181 biomarker, which is currently being proposed as a promising biomarker candidate in various studies.

Blood Test Spots Signs of Alzheimer’s Years Before Symptoms Appear

“Unlike in the clinical phase, however, this marker is not suitable for the early symptom-free phase of Alzheimer’s disease,
” as Klaus Gerwert summarises the results of the comparative study. “Surprisingly, we found that the concentration of glial fibre protein (GFAP) can indicate the disease up to 17 years before the clinical phase, even though it does so much less precisely than the immuno-infrared sensor.” Still, by combining amyloid-beta misfolding and GFAP concentration, the researchers were able to further increase the accuracy of the test in the symptom-free stage to 0,83 AUC.

The Bochum researchers hope that an early diagnosis based on the amyloid-beta misfolding could help to apply Alzheimer’s drugs at such an early stage that they have a significantly better effect – for example, the drug Aduhelm, which was recently approved in the USA. “We plan to use the misfolding test to establish a screening method for older people and determine their risk of developing Alzheimer’s dementia,” says Klaus Gerwert. “The vision of our newly founded start-up betaSENSE is that the disease can be stopped in a symptom-free stage before irreversible damage occurs.” Even though the sensor is still in the development phase, the invention has already been patented worldwide. BetaSENSE aims to bring the immuno-infrared sensor to market and have it approved as a diagnostic device so that it can be used in clinical labs.

Source: https://news.rub.de/

Converting CO2 To Valuable Resources

Enzymes use cascade reactions to produce complex molecules from comparatively simple raw materials. Researchers have now copied this principle.

An international research team has used nanoparticles to convert carbon dioxide into valuable raw materials. Scientists at RUB in Germany and the University of New South Wales in Australia have adopted the principle from enzymes that produce complex molecules in multi-step reactions. The team transferred this mechanism to metallic nanoparticles, also known as nanozymes. The chemists used carbon dioxide to produce ethanol and propanol, which are common raw materials for the chemical industry.

The team led by Professor Wolfgang Schuhmann from the Center for Electrochemistry in Bochum and Professor Corina Andronescu from the University of Duisburg-Essen, together with the Australian team led by Professor Justin Gooding and Professor Richard Tilley, reported in the Journal of the American Chemical Society on 25 August 2019.

Transferring the cascade reactions of the enzymes to catalytically active nanoparticles could be a decisive step in the design of catalysts,” says Wolfgang Schuhmann.

 

Source: https://news.rub.de/

 

Early-Stage Detection Of Alzheimer’s In The Blood

Two major studies with promising antibodies have recently failed – possibly because they have been administered too late. A new very early-detection test gives rise to hope. Using current techniques, Alzheimer’s disease, the most frequent cause of dementia, can only be detected once the typical plaques have formed in the brain. At this point, therapy seems no longer possible. However, the first changes caused by Alzheimer’s take place on the protein level up to 20 years sooner. A two-tier method developed at Ruhr-Universität Bochum (RUB) can help detect the disease at a much earlier stage. The researchers from Bochum published their report in the March 2019 edition of the journal “Alzheimer’s and Dementia: Diagnosis, Assessment and Disease Monitoring”.

This has paved the way for early-stage therapy approaches, where the as yet inefficient drugs on which we had pinned our hopes may prove effective,” says Professor Klaus Gerwert from the Department of Biophysics at RUB.

In Alzheimer’s patients, the amyloid beta protein folds incorrectly due to pathological changes long before the first symptoms occur. A team of researchers headed by Klaus Gerwert successfully diagnosed this misfolding using a simple blood test; as a result, the disease can be detected approximately eight years before the first clinical symptoms occur. The test wasn’t suitable for clinical applications however: it did detect 71 per cent of Alzheimer’s cases in symptomless stages, but at the same time provided false positive diagnoses for nine per cent of the study participants. In order to increase the number of correctly identified Alzheimer’s cases and to reduce the number of false positive diagnoses, the researchers poured a lot of time and effort into optimising the test.

As a result, they have now introduced the two-tier diagnostic method. To this end, they use the original blood test to identify high-risk individuals. Subsequently, they add a dementia-specific biomarker, namely tau protein, to run further tests with those test participants whose Alzheimer’s diagnosis was positive in the first step. If both biomarkers show a positive result, there is a high likelihood of Alzheimer’s disease. “Through the combination of both analyses, 87 of 100 Alzheimer’s patients were correctly identified in our study,” summarises Klaus Gerwert. “And we reduced the number of false positive diagnoses in healthy subjects to 3 of 100. The second analysis is carried out in cerebrospinal fluid that is extracted from the spinal cord.

Now, new clinical studies with test participants in very early stages of the disease can be launched,” points out Gerwert. He is hoping that the existing therapeutic antibodies will still have an effect. “Recently, two major promising studies have failed, especially Crenezumab and Aducanumab – not least because it had probably already been too late by the time therapy was taken up. The new test opens up a new therapy window.”

Source: https://news.rub.de/

Cheap High-Performance Catalysts For Hydrogen Electric Car

The industry has been traditionally deploying platinum alloys as catalysts for oxygen reduction, which is for example essential in fuel cells or metal-air batteries. Expensive and rare, that metal imposes strict restrictions on manufacture. Researchers at Ruhr-Universität Bochum (RUB) and Max-Planck-Institut für Eisenforschung in Germany have discovered an alloy made up of five elements that is noble metal-free and as active as platinum.  The catalytic properties of non-noble elements and their alloys are usually rather poor. To the researchers’ surprise, one alloy made up of five almost equally balanced components offer much better properties. This is because of the so-called high entropy effect. It causes multinary alloys to maintain a simple crystal structure.

Through the interaction of different neighbouring elements, new active centres are formed that present entirely new properties and are therefore no longer bound to the limited properties of the individual elements,” explains Tobias Löffler, PhD student at the RUB Chair of Analytical ChemistryCenter for Electrochemical Sciences headed by Professor Wolfgang Schuhmann. “Our research has demonstrated that this alloy might be relevant for catalysis.”

Headed by Professor Christina Scheu, the research team at the Max-Planck-Institut für Eisenforschung analysed the generated nanoparticles using transmission electron microscopy. RUB chemists determined their catalytic activity and compared it with that of platinum nanoparticles. In the process, they identified a system made of up five elements where the high entropy effect results in catalytic activity for an oxygen reduction that is similar to that of platinum. By optimising the composition further, they successfully improved the overall activity.

These findings may have far-reaching consequences for electrocatalysis in general,” surmises Wolfgang Schuhmann. The researchers are hoping to adapt the properties for any required reactions by taking advantage of the almost infinite number of possible combinations of the elements and modifications of their composition. “Accordingly, the application will not necessarily be limited to oxygen reduction,” says Ludwig. The research team has already applied for a patent.

The results are published in the journal Advanced Energy Materials.

Source: http://news.rub.de/