Cerebrospinal fluid neurogranin in an inducible mouse model of neurodegeneration: A translatable marker of synaptic degeneration

Research output: Contribution to journalArticle

Abstract

Synapse impairment is thought to be an early event in Alzheimer's disease (AD); dysfunction and loss of synapses are linked to cognitive symptoms that precede neuronal loss and neurodegeneration. Neurogranin (Ng) is a somatodendritic protein that has been shown to be reduced in brain tissue but increased in the cerebrospinal fluid (CSF) of AD patients compared to age-matched controls. High levels of CSF Ng have been shown to reflect a more rapid AD progression. To gauge the translational value of Ng as a biomarker, we developed a new, highly sensitive, digital enzyme-linked immunosorbent assay (ELISA) on the Simoa platform to measure Ng in both mouse and human CSF. We investigated and confirmed that Ng levels are increased in the CSF of patients with AD compared to controls. In addition, we explored how Ng is altered in the brain and CSF of transgenic mice that display progressive neuronal loss and synaptic degeneration following the induction of p25 overexpression. In this model, we found that Ng levels increased in CSF when neurodegeneration was induced, peaking after 2 weeks, while they decreased in brain. Our data suggest that CSF Ng is a biomarker of synaptic degeneration with translational value.

Details

Authors
  • Kina Höglund
  • Nathalie Schussler
  • Hlin Kvartsberg
  • Una Smailovic
  • Gunnar Brinkmalm
  • Victor Liman
  • Bruno Becker
  • Henrik Zetterberg
  • Angel Cedazo-Minguez
  • Shorena Janelidze
  • Isabel A. Lefevre
  • Stéphanie Eyquem
  • Oskar Hansson
  • Kaj Blennow
Organisations
External organisations
  • Sahlgrenska Academy
  • Karolinska Institutet
  • Sanofi-Aventis
  • Sahlgrenska University Hospital
  • University College London
  • Skåne University Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurology

Keywords

  • Alzheimer's disease, CSF biomarker, Inducible p25 mice, Neurogranin, SIMOA, Synaptic loss
Original languageEnglish
Article number104645
JournalNeurobiology of Disease
Volume134
Publication statusPublished - 2020 Feb
Publication categoryResearch
Peer-reviewedYes