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

Alzheimers Dement. 2019 Jan;15(1):55-64. doi: 10.1016/j.jalz.2018.08.006. Epub 2018 Oct 12.


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.

Keywords: Alzheimer's disease; CSF biomarker; Differential diagnosis; Enzyme-linked immunosorbent assay; GAP-43.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Biomarkers / cerebrospinal fluid
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • GAP-43 Protein / cerebrospinal fluid*
  • Humans
  • Middle Aged
  • Plaque, Amyloid / cerebrospinal fluid*
  • Plaque, Amyloid / pathology*
  • alpha-Synuclein / cerebrospinal fluid
  • tau Proteins / cerebrospinal fluid*


  • Amyloid beta-Peptides
  • Biomarkers
  • GAP-43 Protein
  • alpha-Synuclein
  • tau Proteins