Abstract.
Alzheimer’s disease (AD) is characterized by the deposition of β-amyloid peptides (Aβ) and a progressive loss of neurons leading to dementia. Because hippocampal neurogenesis is linked to functions such as learning, memory and mood, there has been great interest in examining the effects of AD on hippocampal neurogenesis. This article reviews the pertinent studies and tries to unite them in one possible disease model. Early in the disease, oligomeric Aβ may transiently promote the generation of immature neurons from neural stem cells (NSCs). However, reduced concentrations of multiple neurotrophic factors and higher levels of fibroblast growth factor-2 seem to induce a developmental arrest of newly generated neurons. Furthermore, fibrillary Aβ and down-regulation of oligodendrocyte-lineage transcription factor-2 (OLIG2) may cause the death of these nonfunctional neurons. Therefore, altering the brain microenvironment for fostering apt maturation of graft-derived neurons may be critical for improving the efficacy of NSC transplantation therapy for AD.
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Received 29 January 2008; received after revision 16 March 2008; accepted 18 March 2008
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Waldau, B., Shetty, A.K. Behavior of neural stem cells in the Alzheimer brain. Cell. Mol. Life Sci. 65, 2372–2384 (2008). https://doi.org/10.1007/s00018-008-8053-y
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DOI: https://doi.org/10.1007/s00018-008-8053-y