Alzheimer’s Disease and Adult Neurogenesis—Are Endogenous Stem Cells Part of the Solution?
Alzheimer’s Disease and Adult Neurogenesis—Are Endogenous Stem Cells Part of the Solution?
US Neurology, 2009;5(1):12-4
Abstract
The human brain produces new neurons that mediate hippocampal plasticity but also have a potential role in hippocampal-related disorders, such as Alzheimer’s disease and dementia. Factors such as stress and aging that reduce adult neurogenesis also serve as independent risk factors for Alzheimer’s disease. Causality between loss of neurogenesis and hippocampal dysfunction has not been established; however, neurogenesis is an attractive research avenue for therapy since it is readily modifiable. Activities such as running and enrichment increase the proliferation of neural stem cells and survival of nascent neuroblasts. Adult neurogenesis may alternatively reflect capacity to overcome age-dependent insults and neurodegeneration in the hippocampus. This collectively indicates that stimulation of endogenous cells or transplantation of neural stem cells are potential pathways reversing the behavioral changes associated with neurodegenerative disorders by augmenting structural plasticity of the hippocampus. Continued research in this area and in appropriate animal models of disease is critical for evaluating whether neurogenesis-based therapeutic strategies will have the potential to aid those with degenerative conditions.
Keywords
Adult neurogenesis, neural stem cells, structural plasticity, neurogenic reserve, hippocampus, Alzheimer’s disease, neurodegeneration
Disclosure: The authors have no conflicts of interest to declare.
Received: November 5, 2008 Accepted: June 12, 2009
Correspondence: Paul J Lucassen, PhD, Center for Neuroscience, Swammerdam Institute of Life Sciences, University of Amsterdam, PO Box 94084, 1090 GB Amsterdam, The Netherlands. E: lucassen@science.uva.nl
Numerous clinical trials are under way to evaluate therapeutic approaches to stop the progression of Alzheimer’s disease (AD). Despite the significant efforts toward, for example, clearance of amyloid plaques by vaccination therapies, these approaches may still fall short of cognitive recovery in the AD population as they do not directly focus on the regeneration of damaged tissue and restoration of brain function. Adult neurogenesis is a unique form of structural plasticity in the brain that has important implications in hippocampaldependent learning and behavior. While not shown to have direct links with AD, adult neurogenesis is carefully regulated by various factors, including ones that affect AD, and should be evaluated independently and in relation to Alzheimer’s pathology.
Comprehensive therapy would ideally remove the hallmarks of the disease and provide a level of functional recovery, i.e. by increasing neurogenesis. The therapeutic potential of endogenous neuronal stem cells (NSCs) and grafted stem cells in damaged brain regions should therefore be considered in the context of AD. Although the appropriate delivery of exogenous NSCs to restricted areas of the affected AD brain remains a major challenge, ongoing neurogenesis by endogenous NSCs provides an exciting avenue that has the potential to resolve cognitive deficits in people with AD.
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