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Mol Neurobiol. 2016 Oct;53(8):5796-806. doi: 10.1007/s12035-016-0018-9. Epub 2016 Aug 20.

Early Changes in Hippocampal Neurogenesis in Transgenic Mouse Models for Alzheimer's Disease.

Author information

1
Institute of Molecular Regenerative Medicine, Paracelsus Medical University, Strubergasse 21, 5020, Salzburg, Austria.
2
Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University, Salzburg, Austria.
3
Paul Flechsig Institute for Brain Research, University of Leipzig, Leipzig, Germany.
4
Clinical Neuroscience, Department of Neurology, University of Bonn, Bonn, Germany.
5
Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
6
Institute of Molecular Regenerative Medicine, Paracelsus Medical University, Strubergasse 21, 5020, Salzburg, Austria. ludwig.aigner@pmu.ac.at.
7
Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University, Salzburg, Austria. ludwig.aigner@pmu.ac.at.

Abstract

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in the Western world and is characterized by a progressive loss of cognitive functions leading to dementia. One major histopathological hallmark of AD is the formation of amyloid-beta plaques, which is reproduced in numerous transgenic animal models overexpressing pathogenic forms of amyloid precursor protein (APP). In human AD and in transgenic amyloid plaque mouse models, several studies report altered rates of adult neurogenesis, i.e. the formation of new neurons from neural stem and progenitor cells, and impaired neurogenesis has also been attributed to contribute to the cognitive decline in AD. So far, changes in neurogenesis have largely been considered to be a consequence of the plaque pathology. Therefore, possible alterations in neurogenesis before plaque formation or in prodromal AD have been largely ignored. Here, we analysed adult hippocampal neurogenesis in amyloidogenic mouse models of AD at different points before and during plaque progression. We found prominent alterations of hippocampal neurogenesis before plaque formation. Survival of newly generated cells and the production of new neurons were already compromised at this stage. Moreover and surprisingly, proliferation of doublecortin (DCX) expressing neuroblasts was significantly and specifically elevated during the pre-plaque stage in the APP-PS1 model, while the Nestin-expressing stem cell population was unaffected. In summary, changes in neurogenesis are evident already before plaque deposition and might contribute to well-known early hippocampal dysfunctions in prodromal AD such as hippocampal overactivity.

KEYWORDS:

Alzheimer’s disease; Neural stem- and progenitors; Neurogenesis

PMID:
27544234
PMCID:
PMC5012146
DOI:
10.1007/s12035-016-0018-9
[Indexed for MEDLINE]
Free PMC Article

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