Enhanced neurogenesis in Alzheimer's disease transgenic (PDGF-APP Sw,Ind) mice

Kunlin Jin, Veronica Galvan, Lin Xie, Xiao Ou Mao, Olivia F. Gorostiza, Dale E. Bredesen, David A. Greenberg

Research output: Contribution to journalArticle

359 Citations (Scopus)

Abstract

Neurogenesis continues in the adult brain and is increased in certain pathological states. We reported recently that neurogenesis is enhanced in hippocampus of patients with Alzheimer's disease (AD). We now report that the effect of AD on neurogenesis can be reproduced in a transgenic mouse model. PDGF-APPSw,Ind mice, which express the Swedish and Indiana amyloid precursor protein mutations, show increased incorporation of BrdUrd and expression of immature neuronal markers in two neuroproliferative regions: the dentate gyrus and subventricular zone. These changes, consisting of ≈2-fold increases in the number of BrdUrd-labeled cells, were observed at age 3 months, when neuronal loss and amyloid deposition are not detected. Because enhanced neurogenesis occurs in both AD and an animal model of AD, it seems to be caused by the disease itself and not by confounding clinical factors. As neurogenesis is increased in PDGF-APPSw,Ind mice in the absence of neuronal loss, it must be triggered by more subtle disease manifestations, such as impaired neurotransmission. Enhanced neurogenesis in AD and animal models of AD suggests that neurogenesis may be a compensatory response and that measures to enhance neurogenesis further could have therapeutic potential.

Original languageEnglish
Pages (from-to)13363-13367
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number36
DOIs
StatePublished - 7 Sep 2004

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Neurogenesis
Alzheimer Disease
Animal Models
Amyloid beta-Protein Precursor
Lateral Ventricles
Dentate Gyrus
Amyloid
Synaptic Transmission
Transgenic Mice
Hippocampus
Mutation
Brain

Cite this

Jin, Kunlin ; Galvan, Veronica ; Xie, Lin ; Mao, Xiao Ou ; Gorostiza, Olivia F. ; Bredesen, Dale E. ; Greenberg, David A. / Enhanced neurogenesis in Alzheimer's disease transgenic (PDGF-APP Sw,Ind) mice. In: Proceedings of the National Academy of Sciences of the United States of America. 2004 ; Vol. 101, No. 36. pp. 13363-13367.
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Enhanced neurogenesis in Alzheimer's disease transgenic (PDGF-APP Sw,Ind) mice. / Jin, Kunlin; Galvan, Veronica; Xie, Lin; Mao, Xiao Ou; Gorostiza, Olivia F.; Bredesen, Dale E.; Greenberg, David A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 36, 07.09.2004, p. 13363-13367.

Research output: Contribution to journalArticle

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