Cortical axon sub-population maintains density, but not turnover, of en passant boutons in the aged APP/PS1 amyloidosis model

• Published in: Neurobiology of aging 2022-07, Vol.115, p.29-38
• Main Authors: Fulopova, B., Bennett, W., Summers, B.S., Stuart, K.E., King, A.E., Vickers, J.C., Canty, A.J.
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Axonal boutons; Dementia; Environmental enrichment; Live imaging; Neuroplasticity
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2022.03.007

•We investigated cortical axon en passant boutons (EPB) in the APP/PS1 and wildtype (WT) mouse brain.•Synapse density and inter-EPB distance are maintained across the lifespan in APP/PS1 and WT cortex.•Midlife environmental enrichment does not alter EPB density or inter-EPB distance in APP/PS1 or WT.•EPB turnover (gains and losses) in cortical axons is lower in APP/PS1 axons compared to WT. Synaptic dysfunction is one of the key mechanisms associated with cognitive deficits observed in Alzheimer's disease (AD), yet little is known about the presynaptic axonal boutons in AD. Focusing on cortical en passant boutons (EPBs) along axons located in the motor, sensory and prefrontal regions of the cerebral cortex in the APP/PS1 mouse model of AD, we investigated structural properties of EPBs over the lifespan and in response to a midlife environmental enrichment (EE) intervention. At 3, 12, and 18-22 months and following 6 months of midlife EE, we found that EPBs showed remarkable resilience in preserving overall synaptic output, as evidenced by the maintained density of EPBs along the axon shaft across all experimental conditions. Using cranial window imaging to monitor synaptic changes in real time, we report that despite maintaining a stable synaptic density, the dynamic fraction (gains and losses) of EPBs was significantlyreduced at 10-13 months of age in APP/PS1 axons compared to age matched controls.