학술논문

An accurate fully automated panel of plasma biomarkers for Alzheimer's disease
Document Type
Source
Alzheimer's and Dementia MultiPark: Multidisciplinary research focused on Parkinson´s disease. 19(4):1204-1215
Subject
Alzheimer's disease
amyloid beta
apolipoprotein E
area under the curve
blood
cerebrospinal fluid
clinical practice
cognitively unimpaired
diagnostics
Elecsys
fully automated instruments
glial fibrillary acidic protein
immunoassays
implementation
mild cognitive impairment
neurofilament light
phosphorylated tau
plasma
prediction
prognostics
Medicin och hälsovetenskap
Medicinska och farmaceutiska grundvetenskaper
Neurovetenskaper
Medical and Health Sciences
Basic Medicine
Neurosciences
Language
English
ISSN
1552-5260
Abstract
Introduction: There is a great need for fully automated plasma assays that can measure amyloid beta (Aβ) pathology and predict future Alzheimer's disease (AD) dementia. Methods: Two cohorts (n = 920) were examined: Panel A+ (n = 32 cognitively unimpaired [CU], n = 106 mild cognitive impairment [MCI], and n = 89 AD) and BioFINDER-1 (n = 461 CU, n = 232 MCI). Plasma Aβ42/Aβ40, phosphorylated tau (p-tau)181, two p-tau217 variants, ApoE4 protein, neurofilament light, and GFAP were measured using Elecsys prototype immunoassays. Results: The best biomarker for discriminating Aβ-positive versus Aβ-negative participants was Aβ42/Aβ40 (are under the curve [AUC] 0.83–0.87). Combining Aβ42/Aβ40, p-tau181, and ApoE4 improved the AUCs significantly (0.90 to 0.93; P< 0.01). Adding additional biomarkers had marginal effects (ΔAUC ≤0.01). In BioFINDER, p-tau181, p-tau217, and ApoE4 predicted AD dementia within 6 years in CU (AUC 0.88) and p-tau181, p-tau217, and Aβ42/Aβ40 in MCI (AUC 0.87). Discussion: The high accuracies for Aβ pathology and future AD dementia using fully automated instruments are promising for implementing plasma biomarkers in clinical trials and clinical routine.