Includes several studies demonstrating that post-translational modifications of p53 conformational variants are associated with the pathogenesis of Alzheimer’s disease
MILAN, April 28, 2022 /PRNewswire/ — SpA tiaraa company developing the first blood test for the early prediction of Alzheimer’s disease (AD) progression, today announced the publication of a new peer-reviewed publication, Post-translational modifications of the p53 protein and impact in Alzheimer’s disease: a review of the literaturein the current issue of the journal Frontiers of the neurosciences of aging. The article reviews the abundant scientific literature that explains how post-translational modifications (PTMs) of the protein are associated with the development of Alzheimer’s disease. Diadem exploits the relationship between conformational variants of p53 and Alzheimer’s disease to develop blood-based prognostic and diagnostic tests for Alzheimer’s disease. Its most advanced product, the AlzoSure® The Predict test is a simple, non-invasive plasma biomarker test to accurately predict whether or not a patient with asymptomatic mild cognitive impairment will progress to Alzheimer’s dementia up to six years before the disease manifests fully.
Study author Rakez Kayed, PhD, professor and John Sealy Chair for Parkinson’s Disease Research at the Mitchell Center for Neurodegenerative Disorders at the University of Texas Medical Branch at Galveston, commented. “Growing evidence suggests that certain conformational variants and post-translational modifications of the p53 protein may contribute to the development of Alzheimer’s disease. This review aims to summarize what researchers have found to date about the transformation of p53 into variants and PTMs that impact amyloid, tau, and other pathways involved in neurodegenerative processes that ultimately result in symptomatic Alzheimer’s disease. This knowledge contributes to our growing understanding of the pathophysiology of Alzheimer’s disease, as well as to the development of new prognostic and diagnostic biomarker tests that could enable the use of more effective therapeutic interventions earlier in the disease process. .”
In the new publication, the authors note that the protein p53, known as “the guardian of the genome” for its role in cancer, plays various roles in the maintenance of cellular function, and that changes in the functional activity of the protein can affect its downstream impact. The p53 protein has more recently attracted attention for its possible role in the early progression of Alzheimer’s disease, in part through its involvement in the regulation of oxidative stress, which is a critical factor in the initiation and progression of the MA. Oxidative stress also has a strong relationship with amyloid β and tau-induced neurotoxicity, fueling feedback loops that can accelerate disease progression.
The review focuses on post-translational modifications of p53, which are considered to be the most widespread and efficient cellular mechanisms controlling p53 function. PTMs affect the conformation of p53, increasing its ability to adopt multiple structural and functional states. A number of these are implicated in the development of AD, including functional dysregulation and loss of function in cellular response pathways. The authors also cite several studies showing that conformational unfolding of p53 impacts its role, directly increasing or decreasing the activation of specific pathways associated with Alzheimer’s disease. They conclude that there is significant evidence supporting the potential role of p53 PTMs in the pathogenesis of Alzheimer’s disease and recommend further studies to further elucidate the mechanisms of PTMs and their involvement in the development of AD.
Paul Kinnon, CEO of Diadem, said: “Our AlzoSure blood test for the early prediction of Alzheimer’s disease is based on decades of research into the role of p53 and its conformational variants in the development of Alzheimer’s disease. Alzheimers. This new publication adds to the growing evidence that loss of p53 function via post-translational modifications of the linear sequence of the protein can lead to upstream and downstream effects on amyloid and tau metabolism, as well as on other pathways involved in the pathogenesis of AD. our clinical studies showing that AlzoSure® Predict can identify whether or not individuals will progress to Alzheimer’s dementia years before the disease is fully symptomatic.”
AlzoSure® Predict is a non-invasive biomarker blood test that can identify with high accuracy whether or not people over 50 with signs of cognitive impairment will progress to Alzheimer’s disease up to six years before definitive symptoms appear. . Its usefulness is supported by clinical data from a large longitudinal study this was the basis of AlzoSure® Predict’s recent CE-IVD marking, which allows the test to be marketed in the EU, as well as for a Breakthrough Device designation from the US Food & Drug Administration. The company’s technology uses an analytical method that includes a patented antibody developed by Diadem and designed to bind to U-p53A-Z and its target sequences. U-p53A-Z is a conformational variant of the p53 protein that has been implicated in the pathogenesis of AD in several studies.
About Alzheimer’s Disease
There are approximately 50 million people with dementia worldwide. Alzheimer’s disease is the most common form and represents 60 to 70% of cases. Currently, there are no modifying treatments for Alzheimer’s disease and therapies to treat symptoms are limited. There are about 10 million new cases per year, and the incidence is increasing rapidly as the population ages. The current total cost of care is enormous – estimated at $1 trillion per year in the United States and is expected to double by 2030. Currently, diagnosis of Alzheimer’s disease is slow, inconclusive, invasive and expensive. The development of effective therapies for Alzheimer’s disease has been hampered by the lack of accurate and cost-effective prognosis and diagnostic methods.
Diadem was founded as a spin-out from the University of Brescia (Italy). The company is developing the first blood prognostic test for the early detection of dementia, with a focus on Alzheimer’s disease. The lack of accurate, accessible and affordable diagnostic tools is a major contributor to the lack of effective treatments for this devastating disease. As a result, patients are only diagnosed late in the disease, when effective treatment is no longer possible. Diadem’s rapid, accurate, and cost-effective prognostic blood test makes it possible for the first time to identify patients early in the disease process, when effective interventions and better outcomes are much more achievable. The utility of the approach has been demonstrated in longitudinal clinical studies that served as the basis for the award of CE-IVD marking in the EU and Breakthrough Device designation in the United States. Further retrospective and prospective clinical trials are underway to further validate the clinical claims and support widespread adoption. and uses. Diadem prepares the commercialization of AlzoSure® Plan in collaboration with global strategic partners. The company is also developing AlzoSure® Confirm, a blood diagnostic test for AD that has shown promising results in early studies. For more information, visit diademdx.com/.
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SOURCE Diadem SpA