Alzheimer's disease biomarker-guided diagnostic workflow using the added value of six combined cerebrospinal fluid candidates: Aβ1-42, total-tau, phosphorylated-tau, NFL, neurogranin, and YKL-40

Abstract

Introduction: The diagnostic and classificatory performances of all combinations of three core (amyloid β peptide [i.e., Aβ_1-42], total tau [t-tau], and phosphorylated tau) and three novel (neurofilament light chain protein, neurogranin, and YKL-40) cerebrospinal fluid biomarkers of neurodegeneration were compared among individuals with mild cognitive impairment (n = 41), Alzheimer's disease dementia (ADD; n = 35), frontotemporal dementia (FTD; n = 9), and cognitively healthy controls (HC; n = 21), using 10-fold cross-validation.

Methods: The combinations ranking in the top 10 according to diagnostic accuracy in differentiating between distinct diagnostic categories were identified.

Results: The single biomarkers or biomarker combinations generating the best area under the receiver operating characteristics (AUROCs) were the following: the combination [amyloid β peptide + phosphorylated tau + neurofilament light chain] for distinguishing between ADD patients and HC (AUROC = 0.86), t-tau for distinguishing between ADD and FTD patients (AUROC = 0.82), and t-tau for distinguishing between FTD patients and HC (AUROC = 0.78).

Conclusions: Novel and established cerebrospinal fluid markers perform with at least fair accuracy in the discrimination between ADD and FTD. The classification of mild cognitive impairment individuals was poor.

Keywords: Alzheimer's disease; Alzheimer's disease dementia; Biomarker combination; Cerebrospinal fluid; Clinical diagnosis; Cognitive aging; Diagnostic biomarkers; Frontotemporal dementia; Mild cognitive impairment; Neurodegeneration; Neurofilament light chain; Neurogranin; Pathophysiological pathways; Precision medicine; YKL-40.