PNAS: Cambridge University designs new antibody to accurately identify Alzheimer's disease

Introduction: It is now accepted that Alzheimer's disease is the result of a combination of genes, lifestyle and environmental factors, in part due to specific genetic changesBut the exact cause is not yet clearAlzheimer's disease is a degenerative disease of the nervous system, and no drug has been approved to alter the course of Alzheimer's diseaseResearchers at the University of Cambridge have found a way to design antibodies that can identify toxic particles that destroy healthy brain cells, a potential development in the fight against Alzheimer's diseasedementia is one of the leading causes of death in the UK, costing more than 26 billion pounds a year and is expected to double in the next 25 yearsIt is estimated that the current cost of the global economy due to dementia is close to 1 trillion pounds a yearthe symptoms and causes of Alzheimer's disease
Alzheimer's is one of the most common forms of dementia, leading to brain nerve cell death, tissue defects, memory loss, personality changes and daily mobility disordersscientists have found that abnormal protein clumps, known as oligomers, are the most likely cause of dementia, which has been identified by scientists as likely to cause dementiaAlthough proteins are normally responsible for important cellular processes, according to the amyloid hypothesis, when people develop Alzheimer's disease, these proteins (especially beta-amyloid) become rogue and kill healthy nerve cellsan antibody designedresearchers have found a way to design antibodies that can identify toxic particles that destroy healthy brain cells, a potential advance in the fight against Alzheimer's diseasetheir methods were able to identify these toxic particles, known as beta-amyloid oligomers, and beta-amyloid oligomers are signs of disease, hoping to develop new diagnostic methods to treat Alzheimer's disease and other forms of dementiaa team from the Universities of Cambridge, University College London and Lund University designed an antibody that can detect and quantify toxic oligomers with high accuracyTheir findings were published in the Proceedings of the National Academy of Sciences (PNAS)Professor Michele Vendruscolo, of the Centre for Misfolded Diseases at the University of Cambridge, who led the study, said: "We urgently need quantitative methods to identify oligopolymers that play an important role in Alzheimer's disease, but it is difficult to achieve a standard antibody discovery strategy." Using innovative design strategies, we now identify antibodies that identify these toxic particlesdesign ingress antibodies for specific epitopes in disordered proteinsThe combination and specificity of the designed antibody (DesAb)proteins need to be tightly regulated to function properly, and when this quality control process fails, they are misfolded, triggering a chain reaction that can lead to the death of brain cellsThe misfolded protein forms an abnormal cluster called a plaque that gathers between brain cells, preventing the brain cells from signaling normallyDying brain cells also contain chains of entangled proteins that can disrupt a vital cell transfer system, meaning that the supply of nutrients and other necessities will no longer be transmitted through cellsthere are more than 400 clinical trials for Alzheimer's disease, but none of the drugs approved can change the course of Alzheimer's diseaseDementia is the only disease in the UK that cannot be avoided, hindered or slowed down"While the assumption of amyloid is a common view, it has not been fully validated, in part because beta-amyloid oligomers are difficult to detect, so there are many different views on the causes of Alzheimer's disease," said,Therefore, the discovery of an antibody that is precisely targeted to oligomers is an important step in monitoring the disease's progression, determining its cause and ultimately controlling the diseasethe lack of detection of oligopolymershas been a major obstacle to progress in Alzheimer's researchThis hinders the development of effective diagnosis and treatment interventions and leads to uncertainty about the amyloid hypothesisDr Francesco Aprile, lead author of thestudy, said: "Oligopolymers are difficult to detect, isolate and study, and our method allows the production of antibody molecules, which, although they are heterogeneous, can target oligomers, which we hope may be an important step towards a new diagnostic approach." method, an antibody discovery method developed over the past 10 years at the Center for Misfoldd Diseases, is based on the computational assembly of antibody-antigens, enabling the design of highly challenging antigen antibodies, such as those that only survive for a short period of time through a reasonable design strategy that targets specific areas or epitopes of oligomers, as well as extensive in vitro and in vitro experiments, researchers have designed an antibody whose affinity to oligomers is at least three orders of magnitude higher than other forms of beta-amyloid protein This difference is a key feature that enables antibodies to specifically quantify oligomers in both in vitro and in vivo samples research outlook
the team hopes the tool will help identify better drug candidates and design better clinical trials to help people affected by the disease They also co-founded Wren Therapeutics, a derivative biotech company based in The Health Chemical Incubator, which recently opened the Health Chemical Building, and their task is to put the ideas put forward by the University of Cambridge into practice, looking for new drugs to treat Alzheimer's and other protein misfolding disorders the antibody has been patented by Cambridge Enterprise, Cambridge University's commercialdivision