Development of thresholds and a visualization tool for use of a blood test in routine clinical dementia practice
Inge M.W. Verberk, Jolien Jutte, Maurice Y. Kingma, Sinthujah Vigneswaran, Mariam Gouda, Marie‐Paule van Engelen, Daniel Alcolea, Javier Arranz, Juan Fortea, Alberto Lleó, Claire Chevalier, Moira Marizzoni, Elsmarieke van de Giessen, Afina W. Lemstra, Yolande A.L. Pijnenburg, Wiesje M. van der Flier, Anouk den Braber, David Wilson, Martijn C. Schut, Argonde C. van Harten, Charlotte E. Teunissen
Abstract
INTRODUCTION: We developed a multimarker blood test result interpretation tool for the clinical dementia practice, including phosphorylated (P-)tau181, amyloid-beta (Abeta)42/40, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL). METHODS: We measured the plasma biomarkers with Simoa (n = 1199), applied LASSO regression for biomarker selection and receiver operating characteristics (ROC) analyses to determine diagnostic accuracy. We validated our findings in two independent cohorts and constructed a visualization approach. RESULTS: P-tau181, GFAP, and NfL were selected. This combination had area under the curve (AUC) = 83% to identify amyloid positivity in pre-dementia stages, AUC = 87%-89% to differentiate Alzheimer's or controls from frontotemporal dementia, AUC = 74%-76% to differentiate Alzheimer's or controls from dementia with Lewy bodies. Highly reproducible AUCs were obtained in independent cohorts. The resulting visualization tool includes UpSet plots to visualize the stand-alone biomarker results and density plots to visualize the biomarker results combined. DISCUSSION: Our multimarker blood test interpretation tool is ready for testing in real-world clinical dementia settings. HIGHLIGHTS: We developed a multimarker blood test interpretation tool for clinical dementia practice. Our interpretation tool includes plasma biomarkers P-tau, GFAP, and NfL. Our tool is particularly useful for Alzheimer's and frontotemporal dementia diagnosis.