title: Early Changes in Hippocampal Neurogenesis in Transgenic Mouse Models for Alzheimer's Disease.
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.
authors.affiliation: Institute of Molecular Regenerative Medicine, Paracelsus Medical University, Strubergasse 21, 5020, Salzburg, Austria.|Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University, Salzburg, Austria.
authors.forename: M S
authors.initials: MS
authors.lastname: Unger
authors.affiliation: Institute of Molecular Regenerative Medicine, Paracelsus Medical University, Strubergasse 21, 5020, Salzburg, Austria.|Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University, Salzburg, Austria.
authors.forename: J
authors.initials: J
authors.lastname: Marschallinger
authors.affiliation: Institute of Molecular Regenerative Medicine, Paracelsus Medical University, Strubergasse 21, 5020, Salzburg, Austria.|Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University, Salzburg, Austria.
authors.forename: J
authors.initials: J
authors.lastname: Kaindl
authors.affiliation: Paul Flechsig Institute for Brain Research, University of Leipzig, Leipzig, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Höfling
authors.affiliation: Paul Flechsig Institute for Brain Research, University of Leipzig, Leipzig, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Rossner
authors.affiliation: Clinical Neuroscience, Department of Neurology, University of Bonn, Bonn, Germany.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Heneka
authors.affiliation: Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
authors.forename: A
authors.initials: A
authors.lastname: Van der Linden
authors.affiliation: Institute of Molecular Regenerative Medicine, Paracelsus Medical University, Strubergasse 21, 5020, Salzburg, Austria. ludwig.aigner@pmu.ac.at.|Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University, Salzburg, Austria. ludwig.aigner@pmu.ac.at.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Aigner
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D002452:Cell Count; D019070:Cell Lineage; D049109:Cell Proliferation; D002470:Cell Survival; D018891:Dentate Gyrus / Q000473:pathology; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005260:Female; D006624:Hippocampus / Q000473:pathology*; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D055495:Neurogenesis; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009479:Neuropeptides / Q000378:metabolism; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology
chemical_list: C000714328:DCX protein, human; C000714847:Dcx protein, mouse; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides
keywords: Alzheimer’s disease; Neural stem- and progenitors; Neurogenesis