Fibrinogen-Derived γ377-395 Peptide Improves Cognitive Performance and Reduces Amyloid-β Deposition, without Altering Inflammation, in AβPP/PS1 Mice

J Alzheimers Dis. 2015;47(2):403-12. doi: 10.3233/JAD-142928.

Abstract

Fibrinogen has emerged as a promising therapeutic target against Alzheimer's disease because of its dual role in altered vascular function and amyloid-β aggregation. Here we provide evidence regarding cognitive improvement and reduction of brain parenchyma amyloid-β deposition in AβPP/PS1 mice after treatment for one month with the fibrinogen-blocking peptide Fibγ377-395. No alteration in glial response or other neuroinflammatory markers was observed in the cortex of treated animals. Considering these results and the fact that Fibγ377-395 does not affect coagulation function, this peptide could be considered as a promising and safe candidate for chronic treatment of Alzheimer's disease.

Keywords: Alzheimer’s disease; AβPP/PS1 mice; amyloid; fibrinogen; inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid / drug effects*
  • Amyloid / metabolism
  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / pathology
  • Cerebral Cortex / physiopathology
  • Cognition / drug effects*
  • Cognition / physiology
  • Exploratory Behavior / drug effects
  • Exploratory Behavior / physiology
  • Fibrinogen / metabolism
  • Fibrinogen / pharmacology*
  • Male
  • Mice, Transgenic
  • Neuroglia / drug effects
  • Neuroglia / metabolism
  • Neuroglia / pathology
  • Neuroimmunomodulation / drug effects*
  • Neuroimmunomodulation / physiology
  • Neuroprotective Agents / pharmacology
  • Nootropic Agents / pharmacology*
  • Peptide Fragments / pharmacology*
  • Presenilin-1 / genetics
  • Presenilin-1 / metabolism
  • RNA, Messenger / metabolism
  • Random Allocation

Substances

  • APP protein, human
  • Amyloid
  • Amyloid beta-Protein Precursor
  • Neuroprotective Agents
  • Nootropic Agents
  • PSEN1 protein, human
  • Peptide Fragments
  • Presenilin-1
  • RNA, Messenger
  • fibrinogen gamma (377-395)
  • Fibrinogen