RT Journal Article
T1 Dual roles of Aβ in proliferative processes in an amyloidogenic model of Alzheimer's disease.
A1 Baglietto-Vargas, David
A1 Sanchez-Mejias, Elisabeth
A1 Navarro, Victoria
A1 Jimenez, Sebastian
A1 Trujillo-Estrada, Laura
A1 Gomez-Arboledas, Angela
A1 Sanchez-Mico, Maria
A1 Sanchez-Varo, Raquel
A1 Vizuete, Marisa
A1 Davila, Jose Carlos
A1 Garcia-Verdugo, Jose Manuel
A1 Vitorica, Javier
A1 Gutierrez, Antonia
K1 Gliogenesis
K1 Adult neurogenesis
AB Alzheimer's disease is a major neurodegenerative disorder that leads to severe cognitive deficits in the elderly population. Over the past two decades, multiple studies have focused on elucidating the causative factors underlying memory defects in Alzheimer's patients. In this regard, new evidence linking Alzheimer's disease-related pathology and neuronal stem cells suggests that hippocampal neurogenesis impairment is an important factor underlying these cognitive deficits. However, because of conflicting results, the impact of Aβ pathology on neurogenesis/gliogenesis remains unclear. Here, we investigated the effect of Aβ on neuronal and glial proliferation by using an APP/PS1 transgenic model and in vitro assays. Specifically, we showed that neurogenesis is affected early in the APP/PS1 hippocampus, as evidenced by a significant decrease in the proliferative activity due to a reduced number of both radial glia-like neural stem cells (type-1 cells) and intermediate progenitor cells (type-2 cells). Moreover, we demonstrated that soluble Aβ from APP/PS1 mice impairs neuronal cell proliferation using neurosphere cultures. On the other hand, we showed that oligomeric Aβ stimulates microglial proliferation, whereas no effect was observed on astrocytes. These findings indicate that Aβ has a differential effect on hippocampal proliferative cells by inhibiting neuronal proliferation and triggering the formation of microglial cells.
PB Nature Publishing Group
YR 2017
FD 2017-08-30
LK http://hdl.handle.net/10668/11543
UL http://hdl.handle.net/10668/11543
LA en
NO Baglietto-Vargas D, Sánchez-Mejias E, Navarro V, Jimenez S, Trujillo-Estrada L, Gómez-Arboledas A, et al. Dual roles of Aβ in proliferative processes in an amyloidogenic model of Alzheimer's disease. Sci Rep. 2017 Aug 30;7(1):10085.
DS RISalud
RD Jun 1, 2025