RT Conference Proceedings
T1 Microtubule stabilization protects cognitive function and slows down the course of Alzheimer's like pathology in an amyloidogenic mouse model
A1 Sánchez-Varo, Raquel María
A1 Fernández-Valenzuela, Juan José
A1 De Castro Carratalá, Vanessa
A1 Sánchez-Mejías, Elisabeth
A1 Núñez-Díaz, Cristina
A1 Gómez-Arboledas, Ángela
A1 Moreno-González, Inés
A1 Dávila-Cansino, José Carlos
A1 Vitorica Ferrández, Javier
A1 Gutiérrez-Pérez, Antonia
K1 Alzheimer, enfermedad de
K1 Sistema nervioso - Degeneración
AB Cognitive decline in Alzheimer's disease (AD) is highly related to synaptic dysfunction and neuronal loss. In AD, the hyperphosphorylation of tau compromises axonal transport and leads to the generation of dystrophic neurites,  contributing to synaptic impairment. In addition to phospho-tau, AD brains accumulate amyloid-beta. This study evaluated the effect of the brain-penetrant microtubule-stabilizing agent, Epothilone D (EpoD) in the progression of the disease in a double transgenic mouse model of amyloidosis.Young APP/PS1 mice were weekly treated with intraperitoneal injections of EpoD (2 mg/kg) or vehicle solution for 3 months. Memory performance was tested using object-recognition tasks, Y-maze and Morris water maze. EpoD-treated mice improved their performance of cognitive tests, while hippocampal phospho-tau and Aβ levels, especially soluble oligomers, decreased significantly. β/γ-secretase activities were not affected by EpoD in vitro. 	A significant amelioration of synaptic/neuritic pathology was found. Remarkably, EpoD exerted a neuroprotective effect on SOM-interneurons, a highly AD-vulnerable GABAergic subpopulation.In conclusion, EpoD improved microtubule dynamics and axonal transport in an AD-like context, reducing tau and Abeta accumulation, and promoting neuronal and cognitive protection. These results underline the crosstalk between cytoskeleton pathology and proteinopathy. Therefore, microtubule-stabilizing drugs could be candidates for slowing AD progression at both tau and Aβ pathologies.
YR 2020
FD 2020-12-17
LK https://hdl.handle.net/10630/20629
UL https://hdl.handle.net/10630/20629
LA eng
NO Supported by PI18/01557 (to AG) and PI18/01556 (to JV) grants from ISCiii of Spain, co-financed by FEDER funds from European Union, CIBERNED collaborative grant (to AG and JV), and by PPIT.UMA.B1.2017/26 grant (to RSV). Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 28 feb 2026