Focused Ultrasound Blood-Brain Barrier Opening Improves Cognition and Memory in Alzheimer’s Model

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Key Points

  • Researchers conducted a preclinical study investigating how focused ultrasound blood-brain barrier opening leads to improvements in cognition and memory. 
  • Because the treatment allowed Alzheimer’s mice to recover, the group hypothesized that the cognitive improvement was due to increases in synaptic plasticity.
Medical illustration of focused ultrasound being used on a mouse with Alzheimer’s.
Kong C, Ahn JW, Kim S, Park JY, Na YC, Chang JW, Chung S, Chang WS. Long-lasting restoration of memory function and hippocampal synaptic plasticity by focused ultrasound in Alzheimer’s disease. Brain Stimul. 2023 May 19;16(3):857-866. doi: 10.1016/j.brs.2023.05.014.  

Long-Lasting Restoration of Memory Function and Hippocampal Synaptic Plasticity by Focused Ultrasound in Alzheimer’s Disease 

Jin-Woo Chang, MD, PhD, and his colleagues at Yonsei University College of Medicine in Seoul, Korea, recently conducted a preclinical study investigating how focused ultrasound blood-brain barrier opening (BBBO) leads to improvements in cognition and memory in an Alzheimer’s mouse model. 

The team applied BBBO to the hippocampus in five comparative groups of mice: 

  • Microbubbles only in transgenic Alzheimer’s mice 
  • Microbubbles plus focused ultrasound in transgenic Alzheimer’s mice 
  • Microbubbles only in non-Alzheimer’s littermates 
  • Microbubbles plus focused ultrasound in non-Alzheimer’s littermates 
  • Microbubbles only in naïve mice with unaltered immune systems 

The researchers used the Morris water maze and Y-maze tests to test and compare memory and cognitive function. They also used electrical recordings to measure and compare synaptic strength and long-term potentiation (LTP) in the neurons of the target region. Results indicated that a single session of BBBO improved LTP up to 7 weeks post treatment. The treatment also allowed the Alzheimer’s mice to recover lost synaptic strength to the level found in the sham littermates and naïve mice of the same age. 

The group hypothesized that the cognitive improvement in the Alzheimer’s mice that received focused ultrasound BBBO was due to increases in synaptic plasticity, which was facilitated by the treatment. 

“This preclinical research parallels the clinical work being done in Alzheimer’s patients and could lead to a better understanding of the treatment mechanism,” said Kelsie Timbie, PhD, the Foundation’s veterinary programs director and scientific programs manager. 

The experiments were conducted with a Sonic Concepts single element focused ultrasound transducer, intravenously injected DEFINITY microbubbles, a Bruker 9.4 T, 20-cm bore MRI system, and a mouse head coil. 

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