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Alzheimer's-Type Amyloidosis in Transgenic Mice Impairs Survival of Newborn Neurons Derived from Adult Hippocampal Neurogenesis

Verret, Laure and Jankowsky, Joanna L. and Xu, Guilian M. and Borchelt, David R. and Rampon, Claire (2007) Alzheimer's-Type Amyloidosis in Transgenic Mice Impairs Survival of Newborn Neurons Derived from Adult Hippocampal Neurogenesis. Journal of Neuroscience, 27 (25). pp. 6771-6780. ISSN 0270-6474. PMCID PMC4439193. doi:10.1523/JNEUROSCI.5564-06.2007. https://resolver.caltech.edu/CaltechAUTHORS:20170721-064858327

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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1523/JNEUROSCI.5564-06.2007DOIArticle
http://www.jneurosci.org/content/27/25/6771.longPublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4439193PubMed CentralArticle
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.
Funders:
Funding AgencyGrant Number
John Douglas French Alzheimer's FoundationUNSPECIFIED
Agence Nationale pour la Recherche (ANR)UNSPECIFIED
Centre National de la Recherche Scientifique (CNRS)UNSPECIFIED
McKnight Brain InstituteUNSPECIFIED
John Douglas French Alzheimer's FoundationUNSPECIFIED
American Health Assistance FoundationUNSPECIFIED
NIHKO1 AG26144-01
Singer-Polignac FoundationUNSPECIFIED
National Institute on AgingUNSPECIFIED
Subject Keywords:hippocampal neurogenesis; Alzheimer’s disease; dentate gyrus; transgenic mouse; amyloid precursor protein; presenilin 1
Issue or Number:25
PubMed Central ID:PMC4439193
DOI:10.1523/JNEUROSCI.5564-06.2007
Record Number:CaltechAUTHORS:20170721-064858327
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20170721-064858327
Official Citation:Alzheimer's-Type Amyloidosis in Transgenic Mice Impairs Survival of Newborn Neurons Derived from Adult Hippocampal Neurogenesis Laure Verret, Joanna L. Jankowsky, Guilian M. Xu, David R. Borchelt, Claire Rampon Journal of Neuroscience 20 June 2007, 27 (25) 6771-6780; DOI: 10.1523/JNEUROSCI.5564-06.2007
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:79262
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:21 Jul 2017 17:50
Last Modified:15 Nov 2021 17:46

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