The Alzheimer's Association 2024 diagnostic criteria: Generalizability of supporting autopsy evidence

The Alzheimer's Association 2024 (AA-2024) diagnostic criteria permit a biological diagnosis of Alzheimer's disease based on a positive amyloid biomarker alone. This commentary examines the three autopsy analyses underpinning that framework, focusing on their implications for generalizability. The supporting cohorts were enriched for Alzheimer's disease pathology and derived from selected brain-bank populations whose demographic and clinical characteristics differ from the community-dwelling older adults increasingly undergoing biomarker testing. Independent studies have also produced differing estimates of concurrent tau pathology among amyloid-positive asymptomatic individuals. These observations support further validation of biologic diagnostic criteria in representative aging cohorts before widespread application in routine clinical practice.