Stoelting Europe’s Post

Almost all #APOE4homozygotes exhibited #Alzheimerdisease pathology and had significantly higher levels of AD biomarkers from age 55 compared to APOE3 homozygotes. The study concludes that APOE4 homozygotes represent a genetic form of Alzheimer disease, suggesting the need for individualized prevention strategies, clinical trials and treatments. https://lnkd.in/dMSep5C6

Phosphorylated ubiquitin is like a cherry blossom petal on proteins, forming an intricate, functional structure. Phospho-ubiquitin (pUb) is a key molecular marker in the progression of neurodegenerative disorders. Recent studies have established levels of pUb as a clinical pharmacological biomarker for Parkinson's Disease (PD), important for drug discovery. LifeSensors' diverse range of phospho-ubiquitin tools, encompassing various phosphorylation sites and linkage lengths, illuminates the intricate mechanisms underlying protein degradation in PD and Alzheimer's Disease (AD). Explore our neurodegeneration arsenal, facilitating biomarker discovery, drug development, and precision medicine approaches. Learn more here: https://lnkd.in/g7RziSPM #phosphoubiquitin #neurodegeneration #drugdiscovery #ParkinsonsDisease

😀 Daily article sharing. Happy reading! 💥 Title: Unlocking the potential of circulating small extracellular vesicles in neurodegenerative disease through targeted biomarkers and advancements in biosensing ✍ Authors: Saqer Al Abdullah, Ivy Cocklereece, Kristen Dellinger* ⭐ Keywords: Exosomes, biosensing, Alzheimer's disease, Parkinson's disease  📃 Abstract：Neurodegenerative diseases (NDDs) gradually affect neurons impacting both their function and structure, and they afflict millions worldwide. Detecting these conditions before symptoms arise is crucial for better prognosis and duality of life, given that the disease processes often begin years earlier. Yet, reliable and affordable methods to diagnose NDDs in these stages are currently lacking. There’s a growing interest in using circulating extracellular vesicles (EVs), like small EVs (sEVs) also known as exosomes, as potential sources of markers for screening, diagnosing, and monitoring NDDs. This interest stems from evidence showing that these EVs can carry brain pathological proteins implicated in NDD pathology, and they can even traverse the blood-brain barrier. This review focuses on the creation of EVs, particularly sEVs with a size of less than 200 nanometers, methods for isolating sEVs, and recent advancements in biosensor development to detect NDD-related markers found in sEVs. Furthermore, it explores the potential of sEVs in diagnosing four major NDDs: Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and multiple system atrophy (MSA). 🔗 Full text: https://lnkd.in/ddGatbH2  #biomaterials #Exosomes #biosensing Editorial office: ebmxjournal@explorationpub.com

Neurodegenerative diseases are complex and are active areas of therapeutic research and development. Take Alzheimer’s Disease for example. Nearly 7 million people in the United States are estimated to be living with this disease, with a similar number in Europe. Research has shown a link between complement C3 and amyloid beta clearance, and elevated plasma C3 is associated with amyloid pathology. More recently, cerebrospinal fluid complement protein levels were found to correlate with degeneration and glial cell activation biomarkers in patients with Alzheimer’s Disease (Sandoval et al, 2024). At Kypha we are developing point of care multiplex complement assays that can help shine new lights on the role of complement in Alzheimer’s Disease. Find out more at https://lnkd.in/e6tPBAwb #complement #cytokines #clinicaltrials #biomarkers #immunebiomarkers #diagnostics #complementdiagnostics #cytokinediagnostics #immunemonitoring #realtimediagnostics #pointofcare #alzheimers #alzheimersdisease

For neurodegenerative diseases, swift diagnostic timelines are critical. Three datasets from UCSF Memory and Aging Center discovered potential peripheral biomarkers for Frontotemporal Dementia, with positive implications for biomarkers for other neurodegenerative diseases, including Alzheimer’s.    The research suggests that certain genes show significant differential expression in individuals with a genetic variation associated with tauopathy. The discovery of these peripheral blood biomarkers increases the potential for easily collected and non-invasive diagnostic techniques, presenting a cost-effective alternative to PET imaging or cerebrospinal fluid collection.  The datasets can be requested via #ADWorkbench’s FAIR portal: https://bit.ly/4aUjFK3  

Although their exact role in the disease is debated, hardened clumps or "plaques" of a peptide called amyloid-β clog the brains of people with Alzheimer's disease. Many approved and in-development therapies aim to prevent or remove these plaques, but doing so safely has proven challenging. Researchers from RIKEN Center for Brain Science (CBS) in Japan believe they may have discovered an alternative approach to achieving this goal: boosting the activity of the brain's own amyloid-attacking enzyme, neprilysin. Studies have previously shown that mutations that lead to overproduction of neprilysin protect aging mice from plaque formation. Neprilysin pills or injections are not a viable option because they are not able to travel from the bloodstream to the brain. The researchers sought a way to increase production of the enzyme without tinkering with the genes and they discovered the preferred neurotransmitter for reward enhancement, dopamine. When the researchers gave mice with Alzheimer's-like disease a drug called levodopa, a precursor of dopamine often used to treat Parkinson's disease, for three months, the animals showed increased levels of neprilysin, and fewer plaques. It was found that neprilysin levels naturally decrease with age in normal mice, especially in the frontal part of the brain. This may make it a good biomarker for preclinical or at-risk diagnosis of Alzheimer's disease. The findings are promising and could potentially be explored for Alzheimer's patients. However, the authors note that levodopa can have severe side effects, so their next step is to gain a better understanding of how dopamine leads to increased neprilysin in order to find a safer way to boost the enzyme. https://lnkd.in/efE3dts9

🔬 A groundbreaking study by Chuan Qin et al. sheds light on the potential of CAR-T cell therapy in treating neurological autoimmune diseases like neuromyelitis optica spectrum disorder (NMOSD). Their single-cell multi-omics analysis of patients undergoing anti-BCMA CAR T cell treatment revealed fascinating insights into CAR T cell kinetics, function, and immune alterations in the central nervous system. Key findings include the identification of cytotoxic-like CD8+ CAR T cell clones as main effectors in autoimmunity, enhanced chemotaxis of CAR T cells across the blood-CSF barrier, and the suppression of neuroinflammation. Additionally, the study highlighted the distinctive features of CAR T cells in patients with NMOSD compared to those with hematological malignancies, paving the way for optimized immunotherapies for autoimmune disorders. This research not only deepens our understanding of CAR T cell therapy but also offers promising avenues for the future treatment of autoimmune diseases. Kudos to the team for their valuable contributions to advancing precision medicine! 🌟💉🧠 #Immunotherapy #AutoimmuneDiseases #PrecisionMedicine 🧪🔍✨

Blood-brain-immune interface and neurodegenerative disorders The lab have long investigated how blood that leaks into the brain trigger neurologic diseases, essentially by hijacking the brain’s immune system and setting off a cascade of harmful often-irreversible effects that result in damaged neurons. One blood protein in particular—fibrin, normally involved in blood coagulation—is responsible for setting off this detrimental cascade. The process has been observed in conditions as diverse as Alzheimer’s, traumatic brain injury, multiple sclerosis, premature birth, and even COVID-19. However, the team found that the process could be prevented or interrupted by “neutralizing” fibrin to deactivate its toxic properties—an approach that appears to protect against many neurological diseases when tested in animal models. The scientists previously developed a drug, a therapeutic monoclonal antibody, that specifically targets fibrin’s inflammatory properties without affecting its essential role in blood coagulation. This fibrin-targeting immunotherapy has shown, in mice, to protect from multiple sclerosis and Alzheimer’s, and to treat neurological effects of COVID-19. A humanized version of this first-in-class fibrin immunotherapy is already in Phase 1 safety clinical trials by Therini Bio, a biotech company launched to advance discoveries from the lab. #ScienceMission #sciencenewshighlights https://lnkd.in/gN8PqweG

🔴NEW PAPER ALERT "The role of inflammation in neurological disorders: a brief overview of multiple sclerosis, Alzheimer's & Parkinson's disease'", published in Frontiers. Yahveth Cantero-Fortiz Mercè Boada Rovira et al. Neuroinflammation plays a key role in neurodegenerative diseases like multiple sclerosis (MS), Alzheimer’s disease (AD), and Parkinson’s disease (PD). This review summarizes recent research on how inflammation affects these conditions and highlights the potential use of biomarkers for diagnosis and treatment. Findings reveal the mechanisms behind neuroinflammation, the value of biomarkers in distinguishing between diseases, and how this knowledge could shape new therapies. Future research should validate these biomarkers in larger patient groups to improve diagnosis and treatment strategies. Read it 👇: