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Development of thresholds and a visualization tool for use of a blood test in routine clinical dementia practice.
Verberk IMW
,
Jutte J
,
Kingma MY
,
Vigneswaran S
,
Gouda MMTEE
,
van Engelen MP
,
Alcolea D
,
Arranz J
,
Fortea J
,
Lleó A
,
Chevalier C
,
Marizzoni M
,
van de Giessen EM
,
Lemstra AW
,
Pijnenburg YAL
,
van der Flier WM
,
den Braber A
,
Wilson D
,
Schut MC
,
van Harten AC
,
Teunissen CE
.
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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.
Alzheimer's Drug Discovery Foundation (ADDF), #LSHM20106 Health∼Holland, Topsector Life Sciences & Health, 860197 Marie Curie International Training Network, 831434 Innovative Medicines Initiatives 3TR, 101034344 EPND (IMI 2 Joint Undertaking (JU), Pasman stichting, Gieskes-Strijbisfonds, Stichting Dioraphte, Noaber Foundation, Stichting Alzheimer Nederland, Stichting Steun Alzheimercentrum Amsterdam, 1R01AG056850-01A1 Fondo Europeo de Desarrollo Regional, Unión Europea, "Una manera de hacer Europa" National Institutes of Health, R21AG056974 Fondo Europeo de Desarrollo Regional, Unión Europea, "Una manera de hacer Europa" National Institutes of Health, R01AG061566 Fondo Europeo de Desarrollo Regional, Unión Europea, "Una manera de hacer Europa" National Institutes of Health, 20141210 Marató TV3, 044412 Marató TV3, 20142610 Marató TV3, PI21/00791 Instituto de Salud Carlos III, PI14/01126 Instituto de Salud Carlos III, PI17/01019 Instituto de Salud Carlos III, PI20/01473 Instituto de Salud Carlos III, PI13/01532 Instituto de Salud Carlos III, PI16/01825 Instituto de Salud Carlos III, PI18/00335 Instituto de Salud Carlos III, PI19/00882 Instituto de Salud Carlos III, PI18/00435 Instituto de Salud Carlos III, PI22/00611 Instituto de Salud Carlos III, INT19/00016 Instituto de Salud Carlos III, PI17/01896 Instituto de Salud Carlos III, AC19/00103 Instituto de Salud Carlos III, 2017-SGR-547 Generalitat de Catalunya, SLT006/17/125 Generalitat de Catalunya, SLT006/17/119 Generalitat de Catalunya, SLT002/16/408 Generalitat de Catalunya, #10510032120003 ZonMw, #73305095007 ZonMw, RF1 AG061566 NIA NIH HHS , RF1 AG056850 NIA NIH HHS , R21 AG056974 NIA NIH HHS
