Alzheimer’s disease (AD) is now defined as a biological process initiated by Alzheimer’s disease neuropathologic change (ADNPC) occurring even before the onset of symptoms. This updated research framework emphasizes a biological definition of AD, aligning with the approach taken for other neurodegenerative diseases and various medical fields like oncology. This shift towards biological definitions provides objective criteria for the Diagnosis And Staging of AD, integrating recent advancements in biomarker technology to bridge the gap between research and clinical practice. These guidelines are designed to inform the general principles of AD diagnosis and staging based on the latest scientific understanding, rather than dictating specific clinical workflows or treatment protocols.
Early in the disease process, Core 1 biomarkers, such as amyloid positron emission tomography (PET), cerebrospinal fluid (CSF) biomarkers, and precise plasma biomarkers like phosphorylated tau 217, become abnormal. These biomarkers are indicative of ADNPC, reflecting both neuritic plaques and tangles. Critically, an abnormal result from a Core 1 biomarker is sufficient to establish a biological diagnosis of AD and guide clinical decision-making throughout the disease spectrum.
Later in the disease progression, Core 2 biomarkers, including biofluid and tau PET, become relevant. These biomarkers offer valuable prognostic information. When abnormal, Core 2 biomarkers increase the certainty that AD is a contributing factor to a patient’s symptoms and are important for comprehensive staging of AD.
The framework introduces an integrated biological and clinical staging system. This system acknowledges that the relationship between clinical symptoms and biological AD stages can be influenced by common co-pathologies, cognitive reserve, and individual resistance to the disease. This integrated approach allows for a more nuanced and accurate diagnosis and staging of Alzheimer’s disease, reflecting the complex interplay of biological and clinical factors.
In conclusion, the updated criteria redefine Alzheimer’s disease as a biological entity diagnosable through biomarker evidence, even in asymptomatic individuals. This biomarker-centric approach significantly refines the diagnosis and staging of AD, moving towards a more objective and scientifically grounded framework for both research and clinical applications.
