CONCURRENT BEHAVIOURAL ALTERATIONS, HIPPOCAMPAL HYPOACTIVITY AND OLIGODENDROCYTE LINEAGE CHANGES OCCUR IN 3XTG-AD MICE

Alzheimer’s disease (AD) is the most common form of dementia worldwide and is characterized by progressive neuronal degeneration leading to irreversible cognitive impairment. While AD pathology is classically defined by the accumulation of amyloid-β (Aβ) plaques and neurofibrillary tangles composed of hyperphosphorylated tau, increasing evidence suggests that early alterations in glial cells and myelin may precede over neurodegeneration and correlate with cognitive decline.
In this study, the triple transgenic mouse model of AD (3xTg-AD) was compared to wild-type (WT; B6129SF2/J) controls at 6 months of age. Behavioural tests were performed to assess emotional and cognitive alterations. In parallel, immunofluorescence and stereological approaches were used to characterize changes in the oligodendrocyte lineage and neuronal activity in the hippocampus and prefrontal cortex.
Our results show anxiety-like behaviour and neuronal hypoactivation in the hippocampus of 3xTg-AD mice. Immunofluorescence analysis revealed region-specific alterations within the oligodendrocyte lineage, including a significant reduction of immature BCAS-1/CC1+ oligodendrocytes in the dentate gyrus and a decrease in PDGFRα+ oligodendrocyte precursor cells in the prefrontal cortex. Importantly, stereological quantification confirmed a significant reduction in the total number of Olig2+ cells in the dentate gyrus, while no global changes were detected in the prefrontal cortex.
Overall, these findings suggest that early and region-dependent alterations in oligodendrocyte populations occur in 3xTg-AD mice and may contribute to hippocampal dysfunction and behavioural changes, supporting the idea that non-neuronal cellular changes represent an early and relevant component of Alzheimer’s disease pathology.