The study by Bieger highlights the implications of differences between AD diagnostic guidelines. The findings confirming a benign prognosis in cognitively unimpaired individuals with an isolated amyloid biomarker is timely as the 2024 AA revision extends its AD definition to this specific group4, which may increase discrepancy across frameworks. The study underlines the increased prognostic value and reliability of using both -amyloid and tau biomarkers and the irreplaceable role of the clinical prognosis in validating guidelines. In the context of the current trend in the field of neurodegenerative diseases towards defining diseases purely based on protein-centric biological criteria9,10, this study also demonstrates the potential risks associated with moving from clinico-biological to purely biological definitions in terms of diminishing the connection between diagnosis and clinically relevant outcomes. This initiative of comparing the impact of diagnostic frameworks is valuable and should be further encouraged and replicated. The study also emphasizes the significant impact of the lack of consensus on the definition of AD in the field and urges the individual working groups to renew the 2015 joint approach to propose a consensual AD definition.