Alzheimer’s & Dementia | August 3, 2024

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.

Alzheimers Dement. 2024

https://doi.org/10.1002/alz.14088

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.