The Alzheimer's Association Workgroup's revised criteria for diagnosing and staging Alzheimer's disease (AD) emphasize a biological approach, updating the 2018 research framework. This new framework marks AD based on neuropathologic changes rather than clinical symptoms alone, aligning with medical practices that prioritize biological markers for diagnosis. The criteria shift AD diagnosis from requiring both amyloid and tau abnormalities to recognizing an abnormal Core 1 biomarker as sufficient, such as amyloid PET, cerebrospinal fluid (CSF) amyloid-beta (Aβ) ratios, or highly accurate blood-based biomarkers (BBMs). This change, driven by recent advancements in BBMs and new treatment approvals, makes diagnosis more accessible and aims to improve the precision of early-stage detection, particularly as BBMs gain prominence in clinical applications.

The updated criteria introduce a four-stage biological model (Stages A-D) reflecting the disease's progression, from early amyloid abnormalities (Stage A) to advanced tau pathology (Stage D). This staging can be established using either amyloid and tau PET imaging or a combination of T1 fluid markers with tau PET, with each stage offering a progressively detailed view of disease severity. For instance, Stage A is characterized by abnormal amyloid PET and normal tau levels, while Stage D involves high neocortical tau PET abnormalities alongside amyloid pathology. Although PET staging may not be as sensitive as autopsy-based staging, it provides a valuable prognostic tool, offering a practical approach for monitoring AD progression over time.

The criteria encourage the biological staging and diagnosis of AD to support clinical evaluations rather than to replace them. Recommendations include caution in testing cognitively unimpaired individuals outside research and emphasize the importance of understanding biomarker limitations, such as variability due to demographic factors and comorbidities. Moreover, this biological framework highlights the necessity of accurate reference standards and validated biomarkers that reflect the dynamic biological processes of AD. The article concludes by calling for research that includes more diverse, representative cohorts and the development of risk stratification systems to refine the future of AD diagnosis and personalized care.