Splenocytes derived from young WT mice prevent AD progression in APPswe/PSENldE9 transgenic mice

Oncotarget. 2015 Aug 28;6(25):20851-62. doi: 10.18632/oncotarget.4930.

Abstract

Immunosenescence contributes to pathogenesis of Alzheimer's disease (AD) in the elderly. In this study, we explored the effects of young wild type (WT) splenocytes (ySCs) on Alzheimer's disease by transplanting ySCs into APPswe/PSENldE9 transgenic mice. Young WT splenocytes not only prevented AD, but also improved the spatial learning and memory of APPswe/PSENldE9 transgenic mice. Young WT splenocytes enhanced Aβ clearance, decreased astrogliosis and increased systemic growth differentiation factor 11 (GDF11) levels. Splenocytes derived from old AD mouse promoted AD. There was an increased number of regulatory T cells (Tregs) among old AD splenocytes. We suggest that alterations of GDF11 and Tregs are involved in AD progression and that rejuvenation of the immune system is a potential therapeutic strategy in AD.

Keywords: Alzheimer’s disease; GDF11; Gerotarget; Treg; immunosenescence; splenocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology*
  • Alzheimer Disease / therapy*
  • Animals
  • Astrocytes / cytology
  • Behavior, Animal
  • Bone Morphogenetic Proteins / metabolism
  • Cell Transplantation*
  • Disease Models, Animal
  • Disease Progression
  • Exons
  • Growth Differentiation Factors / metabolism
  • Humans
  • Immunohistochemistry
  • Immunosenescence
  • Male
  • Maze Learning
  • Mice
  • Mice, Transgenic
  • Microglia / metabolism
  • Presenilin-1 / genetics
  • Spatial Learning
  • Spleen / cytology*
  • T-Lymphocytes, Regulatory / cytology

Substances

  • Bone Morphogenetic Proteins
  • Gdf11 protein, mouse
  • Growth Differentiation Factors
  • Presenilin-1