TY - JOUR
T1 - Development of thresholds and a visualization tool for use of a blood test in routine clinical dementia practice
AU - Verberk, Inge M.W.
AU - Jutte, Jolien
AU - Kingma, Maurice Y.
AU - Vigneswaran, Sinthujah
AU - Gouda, Mariam M.T.E.E.
AU - van Engelen, Marie Paule
AU - Alcolea, Daniel
AU - Arranz, Javier
AU - Fortea, Juan
AU - Lleó, Alberto
AU - Chevalier, Claire
AU - Marizzoni, Moira
AU - van de Giessen, Elsmarieke M.
AU - Lemstra, Afina W.
AU - Pijnenburg, Yolande A.L.
AU - van der Flier, Wiesje M.
AU - den Braber, Anouk
AU - Wilson, David
AU - Schut, Martijn C.
AU - van Harten, Argonde C.
AU - Teunissen, Charlotte E.
N1 - Publisher Copyright:
© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
PY - 2024/9
Y1 - 2024/9
N2 - 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.
AB - 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.
KW - Alzheimer
KW - biomarker
KW - blood test
KW - dementia
KW - glial fibrillary acidic protein
KW - neurofilament light
KW - phosphorylated tau
KW - plasma
UR - https://www.scopus.com/pages/publications/85200219305
UR - https://www.scopus.com/inward/citedby.url?scp=85200219305&partnerID=8YFLogxK
U2 - 10.1002/alz.14088
DO - 10.1002/alz.14088
M3 - Article
C2 - 39096164
AN - SCOPUS:85200219305
SN - 1552-5260
VL - 20
SP - 6115
EP - 6132
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
IS - 9
ER -