Plasma lipocalin-2 levels in the preclinical stage of Alzheimer's disease

INTRODUCTION: Lipocalin-2 is an acute-phase protein with pleotropic functions that has been implicated in several diseases including Alzheimer's disease (AD). However, it is unknown if circulating lipocalin-2 levels are altered in the preclinical stage of AD, where AD pathology has accumulated but cognition remains relatively intact. METHODS: In this cross-sectional study, we used an immunoassay to measure plasma lipocalin-2 levels in cognitively normal (Clinical Dementia Rating 0) elderly individuals. 38 of 156 subjects were classified as preclinical AD by cerebrospinal fluid criteria. RESULTS: Plasma lipocalin-2 levels were higher in preclinical AD compared with control subjects and associated with cerebrospinal fluid amyloid-beta(42) levels but not cerebrospinal fluid tau or phosphorylated-tau(181) levels. Exploratory analyses revealed that plasma lipocalin-2 was associated with executive function but not episodic memory. DISCUSSION: Collectively, these results raise the possibility that circulating lipocalin-2 is involved early in AD pathogenesis and may represent an early blood biomarker of amyloid-beta pathology.