Journal
CURRENT ALZHEIMER RESEARCH
Volume 9, Issue 9, Pages 1030-1042Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/156720512803569028
Keywords
Abeta; Alzheimer's disease; differentiation; migration; neural progenitor cell; stem cell; transplantation
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Funding
- Sigrid Juselius Foundation
- Academy of Finland
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Enhancement of neurogenesis and stem cell transplantation are potential therapies for neurodegenerative diseases. In Alzheimer's disease (AD) newborn neural cells and the transplanted cells encounter a diseased brain where the accumulation of toxic amyloid-beta (A beta) peptides disturbs normal functions and interactions of brain cells. In addition, AD-linked mutatations in newborn neurons or autologously transplanted neural progenitor cells (NPCs) are likely to affect the fate of these cells. Here we analyzed the effect of AD-linked APdE9 mutant on NPCs in culture and by isolating NPCs from APdE9 transgenic mice and transplanting them into APdE9 and wild type mouse brain. We show that the brain environment in APdE9 mutant mice reduced astrocytic differentiation but increased the survival and migration of NPCs in vivo. APdE9 mutation of NPCs increased neuronal differentiation also in vitro. Instead extracellular A beta(42) peptide decreased the survival, neuronal differentiation and migration of NPCs in vitro, whereas A beta(40) had an opposite effect. NPC transplantation induced brain neurogenesis, which was not altered in A beta burdened APdE9 brain or by APdE9 mutant in NPCs. Thus, AD-linked mutations in newborn neural cells or NPCs do not compromise the utilization of enhanced neurogenesis or autologous NPC transplantation as potential therapies. The results suggest that combining the treatments resulting in reduced A beta(42) and enhanced neurogenesis may be one therapeutic approach to be explored in AD.
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