Blood biomarkers differentiate AD‐related versus non‐AD‐related cognitive deficits
Kelsey R. Sewell, Lauren E. Oberlin, Thomas K. Karikari, Marcos Olvera‐Rojas, Lu Wan, Jill K. Morris, Paul J. Kueck, Xuemei Zeng, Haiqing Huang, George Grove, Yijun Chen, Tara K Lafferty, Anuradha Sehrawat, M. Ilyas Kamboh, Anna L. Marsland, Arthur Kramer, Edward McAuley, Jeffrey M. Burns, Charles H. Hillman, Eric D. Vidoni, Chaeryon Kang, Kirk I. Erickson
Abstract
INTRODUCTION: The utility of blood-based biomarkers for discriminating Alzheimer's disease (AD)-related versus non-AD-related cognitive deficits in preclinical populations remains poorly understood. Here, we tested the capability of blood markers to detect and discriminate variation in performance across multiple cognitive domains in a cognitively unimpaired sample. METHODS: Participants (n = 648, aged 69.9 ± 3.8, 71% female) underwent a comprehensive cognitive assessment and assays for plasma-based biomarkers amyloid beta (Aβ)1-42/1-40 by mass spectrometry, phosphorylated tau (p-tau) 181 and 217, p-tau217/Aβ1-42, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL). RESULTS: Greater p-tau217 was exclusively associated with poorer episodic memory performance (β = -0.11, SE = 0.04, p = .003), and remained so after covarying for NfL. Higher NfL was non-specifically associated with poorer performance across a range of cognitive domains and remained so after covarying for p-tau217. DISCUSSION: Blood-based biomarkers may differentiate non-AD-related versus AD-related cognitive deficits. This characterization will be important for early intervention and disease monitoring for AD. HIGHLIGHTS: There is heterogeneity in the causes of cognitive decline in aging. AD-related blood biomarkers may help characterize these causes. Elevated p-tau217 was exclusively associated with poorer episodic memory. Elevated NfL was associated with poorer cognition in a broad range of domains. Blood biomarkers may help differentiate AD- and non-AD-related cognitive deficits.