Diadem SpA, in partnership with researchers from the University of Texas Medical Branch (UTMB), has presented findings at the 2024 Clinical Trials on Alzheimer's Disease (CTAD) conference, demonstrating the ability of a novel antibody to detect a misfolded form of the p53 protein in brain tissue of Alzheimer's disease (AD) patients. The study highlights the potential of this antibody, U-p53AZ, as a tool for early AD detection and diagnosis.
The research focused on U-p53AZ, a conformational variant of the p53 protein linked to Alzheimer's disease. The team, led by Prof. Rakez Kayed from the Mitchell Center for Neurodegenerative Disorders at UTMB, utilized a U-p53AZ-specific antibody developed by Diadem to identify the presence of this misfolded protein in human brain tissue. This identification provides insights into AD pathology, which could lead to earlier and more accurate diagnoses.
U-p53AZ as a Prognostic Tool
Early detection of cognitive decline and dementia is challenging due to the lack of reliable and affordable biomarkers. The misfolding of the p53 protein, detected by U-p53AZ, has been developed as a potential prognostic tool for AD. Previous studies indicated that measuring U-p53AZ levels in plasma using a proprietary antibody could predict the risk of significant cognitive deterioration in AD. The current study extends these findings by applying the U-p53AZ antibody to brain tissue, further validating its role in AD diagnosis.
Selective Binding in AD Tissues
Researchers applied U-p53AZ to brain samples from various Braak stages to track AD progression. The antibody selectively bound to misfolded p53 in AD tissues, with minimal binding observed in healthy controls. This selective binding suggests that U-p53AZ can differentiate between AD-related p53 misfolding and normal p53 conformations.
Correlation with Tau Pathology
Co-staining with phosphorylated tau (pTau), a key AD marker, reinforced the association between p53 misfolding and tau pathology, suggesting a strong link to AD progression. Prof. Rakez Kayed noted, "The co-localization of misfolded p53 with phosphorylated tau suggests a mechanistic interaction that warrants further investigation, particularly as a target for early diagnostic intervention."
Clinical Implications
Dr. Sam Agus, Chief Medical Officer at Diadem, stated, "Our results demonstrate that U-p53AZ not only identifies a conformation-specific form of p53 linked to Alzheimer's disease but also correlates with disease severity through Braak staging." The study builds upon prior work (Piccirella et al, JPAD, 2022), positioning U-p53AZ as a tool for both early and advanced AD detection. Its potential clinical application in diagnostic settings is significant, especially given its ability to distinguish AD-related p53 misfolding from normal p53 conformations.
