Mouse brain elastography changes with sleep/wake cycles, aging, and Alzheimer's disease

Area of Science:

• Neuroscience
• Biophysics
• Biomedical Engineering

Background:

• Aging and neurodegenerative diseases significantly impact cognitive function.
• In vivo brain biomechanics is a critical area for understanding neurological health.
• Changes in brain tissue properties are linked to physiological states and disease pathology.

Purpose of the Study:

• To investigate changes in brain tissue stiffness during the sleep/wake cycle.
• To examine the effects of aging and Alzheimer's disease on cortical biomechanics.
• To explore the role of the aquaporin-4 water channel in brain tissue elasticity.

Main Methods:

• Utilized reverberant optical coherence elastography (ROCE) for high-resolution elasticity imaging.
• Conducted four-dimensional scans on wildtype mice, aquaporin-4 knockout mice, and APP/PS1 Alzheimer's disease model mice.
• Measured changes in shear wave speed as an indicator of tissue stiffness.

Main Results:

• Cortical tissue softened by approximately 10% in young wildtype mice during anesthesia (sleep state), but this effect diminished with aging and in Alzheimer's models.
• Cortical stiffness increased with age across all mouse lines, with wildtype mice showing the most pronounced age-related changes.
• The loss of the sleep-wake stiffness change was observed in mice lacking aquaporin-4 and in those overexpressing amyloid-beta.

Conclusions:

• Brain tissue biomechanics are dynamic and influenced by physiological state, age, and disease.
• Aquaporin-4 and amyloid-beta pathology disrupt normal age- and state-dependent changes in brain stiffness.
• This study provides novel insights into brain biomechanics, fluid dynamics, and the impact of brain activity on cortical tissue properties.