Two-photon in vivo imaging of synaptic loss in 5XFAD mouse model of Alzheimer’s disease

Synapse loss is one of the main biological correlates of cognitive decline in Alzheimer’s disease (AD), and it occurs long before noticeable neuronal degeneration. Transgenic mice with mutations characteristic of familial forms of AD (FAD) are widely used to model changes in neuronal structure and function. The 5xFAD mouse model is characterized by accelerated formation of the pathogenic amyloid-beta peptide (Aβ) and exhibits pronounced neurodegeneration in the hippocampus and neocortex in the early postnatal period. The 5xFAD model allows studying the mechanisms of AD pathogenesis at all stages of this neurodegenerative disease. We present long-term studies of dendritic spine dynamics revealed using in vivo two-photon microscopy in hybrid mice (5xFAD-M), obtained by crossing 5xFAD mice with the Thy1-EGFP line expressing green fluorescent protein (GFP). Long-term imaging of dendritic segments of pyramidal neurons in layers II–III of the somatosensory cortex revealed a significant reduction in dendritic spine density in 5xFAD-M mice aged 4 to 6.5 months. Dynamic decrease of dendritic spine density is due to a general suppression of their both formation (gain) and elimination (loss), while the number of “stable” spines remains relatively unchanged.