Anti-Inflammatory Gene Therapy Improves Spatial Memory Performance in a Mouse Model of Alzheimer's Disease

J Alzheimers Dis. 2022;85(3):1001-1008. doi: 10.3233/JAD-215270.

Abstract

The immune system plays a critical role in neurodegenerative processes involved in Alzheimer's disease (AD). In this study, a gene-based immunotherapeutic method examined the effects of anti-inflammatory cellular immune response elements (CIREs) in the amyloid-β protein precursor (AβPP) mouse model. Bi-monthly intramuscular administration, beginning at either 4 or 6 months, and examined at 7.5 through 16 months, with plasmids encoding Interleukin (IL)-10, IL-4, TGF-β polynucleotides, or a combination thereof, into AβPP mice improved spatial memory performance. This work demonstrates an efficient gene therapy strategy to downregulate neuroinflammation, and possibly prevent or delay cognitive decline in AD.

Keywords: Alzheimer’s disease; amyloid-β protein precursor; genetic therapy; immunotherapy; interleukin-10; interleukin-4; neuroinflammation; spatial memory; transforming growth factor beta; transgenic mice.

Publication types

  • Letter
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alzheimer Disease / metabolism*
  • Amyloid beta-Protein Precursor / genetics*
  • Animals
  • Anti-Inflammatory Agents*
  • Cognition
  • Disease Models, Animal
  • Female
  • Genetic Therapy*
  • Immunity, Cellular
  • Immunotherapy*
  • Injections, Intramuscular
  • Interleukin-10
  • Interleukin-4
  • Male
  • Mice
  • Mice, Transgenic
  • Spatial Memory / physiology*

Substances

  • Amyloid beta-Protein Precursor
  • Anti-Inflammatory Agents
  • Interleukin-10
  • Interleukin-4