Differential diagnostic performance of a panel of plasma biomarkers for different types of dementia

Introduction: We explored what combination of blood-based biomarkers (amyloid beta [Aβ]1-42/1-40, phosphorylated tau [p-tau]181, neurofilament light [NfL], glial fibrillary acidic protein [GFAP]) differentiates Alzheimer's disease (AD) dementia, frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB). Methods: We measured the biomarkers with Simoa in two separate cohorts (n = 160 and n = 152). In one cohort, Aβ1-42/1-40 was also measured with mass spectrometry (MS). We assessed the differential diagnostic value of the markers, by logistic regression with Wald's backward selection. Results: MS and Simoa Aβ1-42/1-40 similarly differentiated AD from controls. The Simoa panel that optimally differentiated AD from FTD consisted of NfL and p-tau181 (area under the curve [AUC] = 0.94; cohort 1) or NfL, GFAP, and p-tau181 (AUC = 0.90; cohort 2). For AD from DLB, the panel consisted of NfL, p-tau181, and GFAP (AUC = 0.88; cohort 1), and only p-tau181 (AUC = 0.81; cohort 2). Discussion: A combination of plasma p-tau181, NfL, and GFAP, but not Aβ1-42/1-40, might be useful to discriminate AD, FTD, and DLB.