Two‐level diagnostic classification using cerebrospinal fluid YKL‐40 in Alzheimer's disease

Abstract

Introduction: We assessed the diagnostic accuracy of cerebrospinal fluid (CSF) YKL‐40 in discriminating (1) clinical Alzheimer's disease (AD) from cognitively healthy controls (HCs) and frontotemporal dementia (FTD) (level I) and (2) patients stratified by different pathophysiological profiles from HCs and FTD following a novel unbiased/descriptive categorization based on CSF biomarkers, independent of cognitive impairment severity (level II). Methods: YKL‐40 was compared among HCs ( n = 21), mild cognitive impairment ( n = 41), AD ( n = 35), and FTD ( n = 9) (level I) and among HCs ( n = 21), AD pathophysiology (tau and amyloid β) negative ( n = 15), tau positive ( n = 15), amyloid β positive ( n = 13), AD pathophysiology positive ( n = 33), and FTD ( n = 9) (level II). Results: Level I: YKL‐40 discriminated AD from HC and FTD (area under the receiver operating characteristic curves [AUROCs] = 0.69, 0.71). Level II: YKL‐40 discriminated tau‐positive individuals and AD pathophysiology–positive individuals from HC, AD pathophysiology–positive patients from FTD (AUROCs = 0.76, 0.72, 0.73). Discussion: YKL‐40 demonstrates fair performance in distinguishing tau‐positive patients from HCs, suggesting it may aid clinical diagnosis and support a biomarker‐guided pathophysiological stratification.