An accurate fully automated panel of plasma biomarkers for Alzheimer's disease. Issue 4 (11th August 2022)

• Record Type: Journal Article
• Authors: Palmqvist, Sebastian; Stomrud, Erik; Cullen, Nicholas; Janelidze, Shorena; Manuilova, Ekaterina; Jethwa, Alexander; Bittner, Tobias; Eichenlaub, Udo; Suridjan, Ivonne; Kollmorgen, Gwendlyn; Riepe, Matthias; von Arnim, Christine A.F.; Tumani, Hayrettin; Hager, Klaus; Heidenreich, Fedor; Mattsson‐Carlgren, Niklas; Zetterberg, Henrik; Blennow, Kaj; Hansson, Oskar
• Is Part Of: Alzheimer's & dementia. Volume 19:Issue 4(2023)
• Page Start: 1204
• Page End: 1215
• Publication Date: 2022-08-11
• Subjects: 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; Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.12751
• Languages: English
• ISSNs: 1552-5260

Abstract

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.