Intranasal TAT-haFGF Improves Cognition and Amyloid-β Pathology in an AβPP/PS1 Mouse Model of Alzheimer's Disease

J Alzheimers Dis. 2016;51(4):985-90. doi: 10.3233/JAD-151121.

Abstract

Neurotoxic amyloid-β (Aβ) peptide causing cognitive function disabilities is one of the most characteristic pathological features in Alzheimer's disease (AD). A novel fusion protein, TAT-haFGF, was administrated to AβPP/PS1 transgenic mice by intravenous (IV) injection and intranasal (IN) delivery, respectively, for 5 weeks to compare the pharmacodynamics between the two routes of administration. Our results showed that IN administration of TAT-haFGF improved cognition and reduced Aβ plaques more significantly in AβPP/PS1 mice, when compared with IV injection. Our new findings suggest that TAT-haFGF might be a promising new therapy to attenuate AD pathological process.

Keywords: Alzheimer’s disease; AβPP/PS1; TAT; haFGF; intranasal administration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Alzheimer Disease / complications*
  • Alzheimer Disease / genetics
  • Amyloid beta-Protein Precursor / genetics
  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Brain / pathology
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / etiology*
  • Disease Models, Animal
  • Fibroblast Growth Factors / administration & dosage*
  • Gene Products, tat / administration & dosage
  • Humans
  • Injections, Intraventricular
  • Maze Learning / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Movement / drug effects
  • Mutation / genetics
  • Peptide Fragments / administration & dosage
  • Plaque, Amyloid / drug therapy*
  • Plaque, Amyloid / etiology
  • Presenilin-1 / genetics

Substances

  • Amyloid beta-Protein Precursor
  • Gene Products, tat
  • PSEN1 protein, human
  • Peptide Fragments
  • Presenilin-1
  • Fibroblast Growth Factors