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Neuroepithelial cells from metformin‐treated patients exhibit a preconditioned response to metformin in vitro

Francisco‐Alexei Ramirez‐Galvan, Diana‐Angelica Jimenez‐Galaviz, Juan-Ramón Padilla-Mendoza, Rafael Jijon‐Lorenzo, Maria‐del‐Carmen Silva‐Lucero, María del Carmen Cárdenas‐Aguayo

Alzheimer s & Dementia, 2025

Abstract

Abstract Background Type 2 Diabetes (T2D) is highly prevalent in Latin America, particularly in Mexico, with 15.6% of the population affected (ENSANUT 2020, Montoya 2023). T2D increases the risk of complications: hypertension and dementia. Mild Cognitive Impairment (MCI) precedes Alzheimer's dementia, the most common type. Metformin, the primary treatment for T2D, enhances autophagy, a cellular process for recycling primary components. Autophagy impairment is linked to dementia (Nixon 2024). This study utilizes human olfactory neuroepithelial precursor cells (hONE‐NPCs) as a model for neurodegeneration. Olfactory dysfunction is an early indicator of dementia, suggesting that alterations in hONE‐NPCs may reflect early stages of the disease. Method This study included four groups: healthy controls, individuals with cognitive impairment, those with T2D, and with T2D and cognitive impairment (T2D‐MCI). hONE NPCs were isolated from each participant and characterized using Western Blotting and immunocytofluorescence. Blood samples were collected for HbA1c and protein samples for autophagy markers. Participants underwent a MoCA Test by a certified applicator (MXRAMFR710802563‐01), a medical interview to assess metformin treatment history, and an olfactory test. hONE‐NPCs were treated with or without metformin for 24 hours. Protein samples were collected for Western Blotting analysis in three groups in vitro: Diabetes+MCI+Metformin, Diabetes‐MCI‐Metformin, and Control+Metformin.…

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