A positive Alzheimer's blood biomarker is not a diagnosis: the presence-primacy-permission framework for plasma p-tau217

Abstract

Validated plasma phosphorylated tau 217 (p-tau217) assays identify Alzheimer disease pathology with high accuracy. Wider clinical use creates a risk of postanalytic misclassification when pathology is converted directly into a clinical diagnosis or treatment decision. This editorial examines why accuracy relative to amyloid positron emission tomography or cerebrospinal fluid biomarkers does not establish that Alzheimer disease is the principal cause of a patient's cognitive syndrome. It describes three substitutions: pathology for diagnosis, presence for primacy, and diagnosis for treatment eligibility. We propose the presence-primacy-permission framework to distinguish confirmation of pathology from clinical-biological concordance and treatment suitability. Presence requires appropriate patient selection, a validated assay, and context-specific interpretation. Primacy requires integration of cognitive phenotype, trajectory, functional status, neurologic examination, structural imaging, and coexisting pathology. Permission requires assessment of clinical stage, hemorrhagic risk, treatment feasibility, and patient goals. Separate documentation of the biomarker result, syndrome, etiologic attribution, and actionability may reduce premature diagnostic closure while preserving the clinical value of p-tau217.

Abstract of "A positive Alzheimer's blood biomarker is not a diagnosis: the presence-primacy-permission framework for plasma p-tau217" by Bhatia V, Khatak A, https://doi.org/10.1097/ms9.0000000000005661, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.