Light-Sheet Fluorescence Imaging Reveals Three-Dimensional Amyloid Burden Reduction Following Five Weeks of Swimming Exercise in Alzheimer’s Mouse

TL;DR

Swimming exercise in Alzheimer's mice reduced amyloid buildup in the brain, suggesting exercise may help slow dementia progression.

Contribution

This study is the first to use light-sheet fluorescence imaging to show that swimming reduces β-amyloid pathology in late-stage Alzheimer’s mice.

Findings

Swimming mice had significantly lower β-amyloid accumulation volume compared to controls.

No significant differences in plaque shape parameters like ellipticity or sphericity were observed.

The findings suggest swimming can enhance resistance to pathology even in advanced Alzheimer’s stages.

Abstract

Emerging evidence from observational studies suggests that lifestyle modifications, particularly moderate-intensity exercise, may confer neuroprotective benefits against dementia, potentially by enhancing brain resistance through clearance mechanisms. Using light-sheet fluorescence microscopy (LSFM) with tissue clearing, we investigated the role of voluntary swimming in ameliorating β-amyloid pathology in a transgenic Alzheimer’s disease (AD) mouse model. Twenty 52-week-old hAPPsw mice were randomly divided into a 5-week voluntary swimming intervention group and a control group (each n = 10). Each session included a 10-min swim followed by a 10-min rest, escalating from one session per day in the first week to three sessions per day by the fifth week. The excised brains were prepared using tissue-clearing and volume immunostaining with thioflavin-S for β-amyloid. For LSFM imaging, the individual plaque area and volume, total plaque load, and morphological parameters were quantified via an Imaris-based three-dimensional (3D) volumetric surface model. Visual comparison revealed that the intervention group presented significantly lower β-amyloid accumulation. The total surface volume of β-amyloid accumulation in the intervention group was significantly lower than that of the control group (intervention, 122,180,948 μm3 [105,854,660–169,063,081]; control, 167,201,016 μm3 [139,367,765–193,535,450]; p = 0.043). There were no significant differences in the morphological parameters, such as ellipticity and sphericity. Our LSFM study demonstrated notable reductions in β-amyloid, as evidenced by a decrease in total surface volume, in 52-week-old transgenic mice after a 5-week structured swimming program, supporting the notion that even in advanced AD stages, leisure-time voluntary swimming serves as an efficacious intervention for augmenting resistance to pathology.

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