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While the amyloid/tau/neurodegeneration (ATN) framework has found wide application in Alzheimer’s disease research, it is unclear if thresholds obtained using distinct thresholding methods are concordant within the same dataset and interchangeable across cohorts.

To investigate the robustness of data-driven thresholding methods and ATN profiling across cohort datasets.

We evaluated the impact of thresholding methods on ATN profiles by applying five commonly-used methodologies across cohort datasets. We assessed the generalizability of disease patterns discovered within ATN profiles by clustering individuals from different cohorts who were assigned to the same ATN profile.

Participants with available CSF amyloid-β 1–42, phosphorylated tau, and total tau measurements were included from eleven AD cohort studies.

We …