Blood biomarkers differentiate AD-related versus non-AD-related cognitive deficits. Academic Article uri icon

Overview

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.

authors

  • Sewell, Kelsey R
  • Oberlin, Lauren
  • Karikari, Thomas K
  • Olvera-Rojas, Marcos
  • Wan, Lu
  • Morris, Jill K
  • Kueck, Paul J
  • Zeng, Xuemei
  • Huang, Haiqing
  • Grove, George
  • Chen, Yijun
  • Lafferty, Tara K
  • Sehrawat, Anuradha
  • Kamboh, M Ilyas
  • Marsland, Anna L
  • Kramer, Arthur F
  • McAuley, Edward
  • Burns, Jeffrey M
  • Hillman, Charles H
  • Vidoni, Eric D
  • Kang, Chaeryon
  • Erickson, Kirk I

publication date

  • March 1, 2025

Research

keywords

  • Alzheimer Disease
  • Biomarkers
  • Cognitive Dysfunction

Identity

PubMed Central ID

  • PMC11923558

Scopus Document Identifier

  • 105001035501

Digital Object Identifier (DOI)

  • 10.1002/alz.14619

PubMed ID

  • 40110626

Additional Document Info

volume

  • 21

issue

  • 3