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

Leinenga, G; To, XV; Bodea, LG; Yousef, J; Richter-Stretton, G; Palliyaguru, T; Chicoteau, A; Dagley, L; Nasrallah, F; G&#246;tz, J

Author(s): Leinenga, G; To, XV; Bodea, LG; Yousef, J; Richter-Stretton, G; Palliyaguru, T; Chicoteau, A; Dagley, L; Nasrallah, F; Götz, J;
Details: Publication Year 2024-03-18,Volume 29,Issue #8,Page 2408-2423
Journal Title: Molecular Psychiatry
Abstract: A prevalent view in treating age-dependent disorders including Alzheimer's disease (AD) is that the underlying amyloid plaque pathology must be targeted for cognitive improvements. In contrast, we report here that repeated scanning ultrasound (SUS) treatment at 1 MHz frequency can ameliorate memory deficits in the APP23 mouse model of AD without reducing amyloid-β (Aβ) burden. Different from previous studies that had shown Aβ clearance as a consequence of blood-brain barrier (BBB) opening, here, the BBB was not opened as no microbubbles were used. Quantitative SWATH proteomics and functional magnetic resonance imaging revealed that ultrasound induced long-lasting functional changes that correlate with the improvement in memory. Intriguingly, the treatment was more effective at a higher frequency (1 MHz) than at a frequency within the range currently explored in clinical trials in AD patients (286 kHz). Together, our data suggest frequency-dependent bio-effects of ultrasound and a dissociation of cognitive improvement and Aβ clearance, with important implications for the design of trials for AD therapies.
Publisher: Springer Nature
Keywords: Animals; *Amyloid beta-Peptides/metabolism; *Alzheimer Disease/metabolism; Mice; *Blood-Brain Barrier/metabolism; *Mice, Transgenic; *Disease Models, Animal; *Magnetic Resonance Imaging/methods; Memory/physiology; Plaque, Amyloid/metabolism; Male; Memory Disorders/metabolism; Amyloid beta-Protein Precursor/metabolism/genetics; Brain/metabolism/diagnostic imaging; Cognition/physiology
Research Division(s): Advanced Technology And Biology
PubMed ID: 38499653
Publisher's Version: https://doi.org/10.1038/s41380-024-02509-5
Open Access at Publisher's Site: https://doi.org/10.1038/s41380-024-02509-5
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-03-27 08:35:43

Last Modified: 2024-10-03 09:19:51