Clinical Assessment of a Plasma AT(N) Panel for Alzheimer's Disease

1.ImportanceWith the emergence of new therapeutics for treatment of Alzheimers disease, there is currently a critical need for sensitive and accurate blood-based tests to assist with the diagnosis and treatment of Alzheimers disease. ObjectiveTo determine the clinical validity of an analytically validated plasma panel for the assessment of Alzheimers disease. Design, Setting, and ParticipantsThis cross-sectional study measured biomarkers representative of the Alzheimers disease AT(N) framework in 200 plasma specimens acquired from the Australian Imaging, Biomarker & Lifestyle (AIBL) Study of Ageing. Specimens were obtained from amyloid PET negative subjects classified as cognitively unimpaired (n = 75) and amyloid PET positive subjects classified as having no cognitive impairment (n = 49), mild cognitive impairment (n = 26), or Alzheimers disease dementia (n = 50). ExposuresAmyloid PET and plasma A{beta}42/40, pTau181, and NfL. Main Outcomes and MeasuresTo assess the utility of the plasma panel to assess onset and progression of Alzheimers disease with respect to amyloid PET results and cognitive impairment. ResultsA difference was observed for each assay with respect to amyloid status (p<0.0001). Receiver operating characteristic (ROC) analysis of clinical specimen results from validated assays produced an area-under-the-curve (AUC) of 0.941 for A{beta}42/40, 0.847 for pTau181, and 0.666 for NfL (p < 0.0001 for all biomarkers). The sensitivity (96.0%) and specificity (86.7%) observed for A{beta}42/40 measurements meets current recommendations for triage testing. In addition, plasma levels of pTau181 and NfL were also found to increase with worsening cognitive impairment. Conclusions and RelevanceThe clinical concordance with amyloid PET for each biomarker is consistent with the biological progression of the AD continuum. As such, the availability of this AT(N) panel will provide clinicians with a simple blood-based means to provide evidence of AD pathological changes and could help identify AD patients much faster, shorten the overall AD patient diagnostic journey, and enable earlier treatment interventions.