Scanning ultrasound-mediated memory and functional improvements do not require amyloid-β reduction

Area of Science:

• Neuroscience
• Biomedical Engineering
• Gerontology

Background:

• Alzheimer's disease (AD) treatment often focuses on amyloid-beta (Aβ) plaques.
• Current therapeutic strategies aim to reduce Aβ burden for cognitive enhancement.

Purpose of the Study:

• To investigate the efficacy of scanning ultrasound (SUS) in ameliorating memory deficits in a mouse model of AD.
• To explore the effects of SUS on Aβ burden and cognitive function independently.
• To determine the impact of ultrasound frequency on therapeutic outcomes.

Main Methods:

• Utilized the APP23 mouse model of Alzheimer's disease.
• Administered repeated scanning ultrasound (SUS) treatment at 1 MHz frequency without microbubbles.
• Assessed memory deficits and Aβ burden.
• Employed quantitative SWATH proteomics and functional magnetic resonance imaging (fMRI).

Main Results:

• SUS treatment ameliorated memory deficits without reducing Aβ burden.
• Ultrasound induced long-lasting functional brain changes correlated with memory improvement.
• Higher frequency (1 MHz) SUS was more effective than lower frequency (286 kHz).
• Blood-brain barrier (BBB) opening was not required for therapeutic effects.

Conclusions:

• Cognitive improvement in AD can be achieved independently of Aβ clearance.
• Ultrasound exhibits frequency-dependent bio-effects with potential therapeutic applications.
• Findings have significant implications for designing future Alzheimer's disease clinical trials.