ArticleCells2026
NT-3-Expressing Olfactory Ensheathing Cells Reduce Brain Aβ1-42 Accumulation and Improve Cognitive Performance in a Rat Model of Alzheimer's Disease.
Article in Cells, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Cell-based gene therapy is a promising strategy to promote regeneration in Alzheimer's disease (AD). Neurotrophin-3 (NT-3) plays a key role in neuroprotection and brain regeneration, providing a strong rationale for its exogenous delivery. Olfactory ensheathing cells (OECs) have high regenerative potential and serve as a vehicle for local gene delivery. We investigated the therapeutic potential of NT-3-expressing OECs in an Aβ1-42-induced AD model in female Wistar rats. Rat OECs were transduced with an Ad5RGD-CAG-NT-3 adenoviral vector, and NT-3 levels were measured in vitro using ELISA. To evaluate the efficacy of NT-3-transduced and non-transduced OECs, we performed behavioral assessments and measured the concentration of NT-3, Aβ1-42, and pTau levels in brain specimens 4 weeks post-transplantation. Transduced OECs exhibited markedly increased NT-3 secretion in vitro compared with non-transduced cells. All OEC-treated groups showed improved cognitive performance following transplantation. However, only NT-3-transduced OECs significantly increased brain NT-3 and reduced Aβ1-42 levels, indicating an enhanced therapeutic effect mediated by NT-3 overexpression. None of the cell grafts affected pTau levels. These findings demonstrate that OEC transplantation improves functional outcomes in experimental AD, while NT-3 overexpression provides biochemical benefits by reducing amyloid accumulation. Taken together, our findings support further investigation of NT-3-expressing OECs as a cell-based gene therapy for AD.
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