Challenges in the practical implementation of blood biomarkers for Alzheimer's disease.

Blood biomarkers have emerged as accessible, cost-effective, and highly promising tools for advancing the diagnostics of Alzheimer's disease. However, transitioning from cerebrospinal fluid biomarkers to blood biomarkers-eg, to verify amyloid β pathology-requires careful consideration. This Series paper highlights the main challenges in the implementation of blood biomarkers for Alzheimer's disease in different possible contexts of use. Despite the robustness of measuring blood biomarker concentrations, the widespread adoption of blood biomarkers requires rigorous standardisation efforts to address inherent challenges in diverse contexts of use. The challenges include understanding the effect of pre-analytical and analytical conditions, potential confounding factors, and comorbidities that could influence outcomes of blood biomarkers and their use in diverse populations. Additionally, distinct scenarios present their own specific challenges. In memory clinics, the successful integration of blood biomarkers in diagnostic tests will require well-established diagnostic accuracy and comprehensive assessments of the effect of blood biomarkers on the diagnostic confidence and patient management of clinicians. In primary care settings, and even more when implemented in population-based screening programmes for which no experience with any biomarkers for Alzheimer's disease currently exists, the implementation of blood biomarkers will be challenged by the need for education of primary care clinical staff and clear guidelines. However, despite the challenges, blood biomarkers hold great promise for substantially enhancing the diagnostic accuracy and effectively streamlining referral processes, leading to earlier diagnosis and access to treatments. The ongoing efforts that are shaping the integration of blood biomarkers across diverse clinical settings pave the way towards precision medicine in Alzheimer's disease.