Alzheimer's-Type Amyloidosis in Transgenic Mice Impairs Survival of Newborn Neurons Derived from Adult Hippocampal Neurogenesis
Abstract
Alzheimer's disease (AD) is characterized by severe neuronal loss in several brain regions important for learning and memory. Of the structures affected by AD, the hippocampus is unique in continuing to produce new neurons throughout life. Mounting evidence indicates that hippocampal neurogenesis contributes to the processing and storage of new information and that deficits in the production of new neurons may impair learning and memory. Here, we examine whether the overproduction of amyloid-β (Aβ) peptide in a mouse model for AD might be detrimental to newborn neurons in the hippocampus. We used transgenic mice overexpressing familial AD variants of amyloid precursor protein (APP) and/or presenilin-1 to test how the level (moderate or high) and the aggregation state (soluble or deposited) of Aβ impacts the proliferation and survival of new hippocampal neurons. Although proliferation and short-term survival of neural progenitors in the hippocampus was unaffected by APP/Aβ overproduction, survival of newborn cells 4 weeks later was dramatically diminished in transgenic mice with Alzheimer's-type amyloid pathology. Phenotypic analysis of the surviving population revealed a specific reduction in newborn neurons. Our data indicate that overproduction of Aβ and the consequent appearance of amyloid plaques cause an overall reduction in the number of adult-generated hippocampal neurons. Diminished capacity for hippocampal neuron replacement may contribute to the cognitive decline observed in these mice.
Additional Information
© 2007 Society for Neuroscience. Beginning six months after publication the Work will be made freely available to the public on SfN's website to copy, distribute, or display under a Creative Commons Attribution 4.0 International (CC BY 4.0) license (https://creativecommons.org/licenses/by/4.0/). The user may not create, compile, publish, host, enable or otherwise make available a mirror site of The Journal of Neuroscience site This work was supported by grants from the France Alzheimer Association and the Singer-Polignac Foundation (L.V.), the Agence Nationale pour la Recherche and the Centre National de la Recherche Scientifique (C.R.), the McKnight Brain Institute (D.R.B.), the John Douglas French Alzheimer's Foundation (J.L.J.), the American Health Assistance Foundation (J.L.J.), and the National Institute on Aging (KO1 AG26144-01 to J.L.J.). We thank Bob and Julie Switzer at NeuroScience Associates (Knoxville, TN) for providing the MultiBrain Array sectioning and advice on handling these large-format sections. We gratefully acknowledge Dennis Steindler and the McKnight Brain Institute for supporting the completion of our study.Attached Files
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Additional details
- PMCID
- PMC4439193
- Eprint ID
- 79262
- DOI
- 10.1523/JNEUROSCI.5564-06.2007
- Resolver ID
- CaltechAUTHORS:20170721-064858327
- John Douglas French Alzheimer's Foundation
- Agence Nationale pour la Recherche (ANR)
- Centre National de la Recherche Scientifique (CNRS)
- McKnight Brain Institute
- John Douglas French Alzheimer's Foundation
- American Health Assistance Foundation
- KO1 AG26144-01
- NIH
- Singer-Polignac Foundation
- National Institute on Aging
- Created
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2017-07-21Created from EPrint's datestamp field
- Updated
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2021-11-15Created from EPrint's last_modified field