RT Conference Proceedings
T1 Human iPSC-derived APOE4/4 Alzheimer´s disease astrocytes exhibit a proinflammatory and senescent state that compromise neuronal support
A1 García-León, Juan Antonio
A1 Cáceres Palomo, Laura
A1 Sánchez-Mejías, Elisabeth
A1 Trujillo-Estrada, Laura Isabel
A1 López-Oliva, Elba
A1 Moreno-González, Inés
A1 Vitorica, Javier
A1 Gutiérrez-Pérez, Antonia
K1 Alzheimer, Enfermedad de
K1 Astrocitos
AB Background:Alzheimer's disease (AD) is characterized by a complex pathology, not fully resolved yet. Thisfact, together with the lack of reliable models, has impeded the development of effectivetherapies. Glial cell dysfunction has been proposed to be involved in AD pathogenesis, but thiscannot be properly modeled using the available animal models, so we hypothesized that cellsderived from AD patients can serve as a better platform for studying the disease. In this sense,human pluripotent stem cells (hPSC) allow the generation of different types of neural cells,which can be used for disease modeling, identification of new targets and drugs development.Methods:We have generated hiPSC-derived astrocytes from AD patients and cognitively unimpaired agematchedindividuals and evaluated their metabolism and phenotype employing confocalimaging, immunofluorescence, flow cytometry, RT-qPCR and functional assays.Results:All astrocytes expressed functional markers including aldehyde dehydrogenase 1A1(ALDH1A1), glutamate transporter GLAST, glial fibrillary acidic protein (GFAP), aquaporin-4(AQP4) and vimentin. However, astrocytes from AD patients showed increased expression ofreactive markers. In addition, these astrocytes derived from AD patients showed significantmetabolic alterations associated with a pro-inflammatory and senescent phenotype which inturn impair their neuronal support as measured in coculture assays.Conclusions:Our preliminary data suggest that astrocytes derived from AD patients present an intrinsic proinflammatoryand senescent phenotype which compromise their functionality. Elucidating themechanisms inducing these processes and their functional consequences should help for abetter understanding of role that astrocytes play in AD, by direct functioning and also through their interactions with neurons and the other glial cells. This should lead to the identification ofpotential therapeutic targets for future AD treatments.
YR 2025
FD 2025-07-11
LK https://hdl.handle.net/10630/45584
UL https://hdl.handle.net/10630/45584
LA eng
NO Instituto de Salud Carlos III
NO Ciberned
NO Sumaira Foundation
NO IBIMA- Bionand
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 27 feb 2026