Elevated CSF GAP-43 is Alzheimer's disease specific and associated with tau and amyloid pathology

Åsa Sandelius, Erik Portelius, Åsa Källén, Henrik Zetterberg, Uros Rot, Bob Olsson, Jon B. Toledo, Leslie M. Shaw, Virginia M.Y. Lee, David J. Irwin, Murray Grossman, Daniel Weintraub, Alice Chen-Plotkin, David A. Wolk, Leo McCluskey, Lauren Elman, Vesna Kostanjevecki, Manu Vandijck, Jennifer McBride, John Q. TrojanowskiKaj Blennow

Research output: Contribution to journalArticlepeer-review

94 Scopus citations

Abstract

Introduction: The level of the presynaptic protein growth-associated protein 43 (GAP-43) in cerebrospinal fluid (CSF) has previously been shown to be increased in Alzheimer's disease (AD) and thus may serve as an outcome measure in clinical trials and facilitate earlier disease detection. Methods: We developed an enzyme-linked immunosorbent assay for CSF GAP-43 and measured healthy controls (n = 43), patients with AD (n = 275), or patients with other neurodegenerative diseases (n = 344). In a subpopulation (n = 93), CSF GAP-43 concentrations from neuropathologically confirmed cases were related to Aβ plaques, tau, α-synuclein, and TDP-43 pathologies. Results: GAP-43 was significantly increased in AD compared to controls and most neurodegenerative diseases and correlated with the magnitude of neurofibrillary tangles and Aβ plaques in the hippocampus, amygdala, and cortex. GAP-43 was not associated to α-synuclein or TDP-43 pathology. Discussion: The presynaptic marker GAP-43 is associated with both diagnosis and neuropathology of AD and thus may be useful as a sensitive and specific biomarker for clinical research.

Original languageEnglish (US)
Pages (from-to)55-64
Number of pages10
JournalAlzheimer's and Dementia
Volume15
Issue number1
DOIs
StatePublished - Jan 2019

Keywords

  • Alzheimer's disease
  • CSF biomarker
  • Differential diagnosis
  • Enzyme-linked immunosorbent assay
  • GAP-43

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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