title: Neurogenic effects of β-amyloid in the choroid plexus epithelial cells in Alzheimer's disease.
abstract: β-amyloid (Aβ) can promote neurogenesis, both in vitro and in vivo, by inducing neural progenitor cells to differentiate into neurons. The choroid plexus in Alzheimer's disease (AD) is burdened with amyloid deposits and hosts neuronal progenitor cells. However, neurogenesis in this brain tissue is not firmly established. To investigate this issue further, we examined the effect of Aβ on the neuronal differentiation of choroid plexus epithelial cells in several experimental models of AD. Here we show that Aβ regulates neurogenesis in vitro in cultured choroid plexus epithelial cells as well as in vivo in the choroid plexus of APP/Ps1 mice. Treatment with oligomeric Aβ increased proliferation and differentiation of neuronal progenitor cells in cultured choroid plexus epithelial cells, but decreased survival of newly born neurons. These Aβ-induced neurogenic effects were also observed in choroid plexus of APP/PS1 mice, and detected also in autopsy tissue from AD patients. Analysis of signaling pathways revealed that pre-treating the choroid plexus epithelial cells with specific inhibitors of TyrK or MAPK diminished Aβ-induced neuronal proliferation. Taken together, our results support a role of Aβ in proliferation and differentiation in the choroid plexus epithelial cells in Alzheimer's disease.
authors: Neuroscience Group, Instituto de Investigacion Hospital, 12 de Octubre, Av. de Córdoba s/n. 28041, Madrid, Spain.
authors: Marta
authors: M
authors: Bolos
authors: Carlos
authors: C
authors: Spuch
authors: Lara
authors: L
authors: Ordoñez-Gutierrez
authors: Francisco
authors: F
authors: Wandosell
authors: Isidro
authors: I
authors: Ferrer
authors: Eva
authors: E
authors: Carro
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001973:Bromodeoxyuridine; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002831:Choroid Plexus / Q000166:cytology* / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000187:drug effects; D055495:Neurogenesis / Q000187:drug effects*; D016133:Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D001973:Bromodeoxyuridine