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Blood-brain barrier opening in Alzheimer's disease using MR-guided focused ultrasound.

Nir Lipsman | Ying Meng | Allison J Bethune | Yuexi Huang | Benjamin Lam | Mario Masellis | Nathan Herrmann | Chinthaka Heyn | Isabelle Aubert | Alexandre Boutet | Gwenn S Smith | Kullervo Hynynen | Sandra E Black
Nature communications | 2018

Magnetic resonance-guided focused ultrasound in combination with intravenously injected microbubbles has been shown to transiently open the blood-brain barrier, and reduce beta-amyloid and tau pathology in animal models of Alzheimer's disease. Here, we used focused ultrasound to open the blood-brain barrier in five patients with early to moderate Alzheimer's disease in a phase I safety trial. In all patients, the blood-brain barrier within the target volume was safely, reversibly, and repeatedly opened. Opening the blood-brain barrier did not result in serious clinical or radiographic adverse events, as well as no clinically significant worsening on cognitive scores at three months compared to baseline. Beta-amyloid levels were measured before treatment using [18F]-florbetaben PET to confirm amyloid deposition at the target site. Exploratory analysis suggested no group-wise changes in amyloid post-sonication. The results of this safety and feasibility study support the continued investigation of focused ultrasound as a potential novel treatment and delivery strategy for patients with Alzheimer's disease.

Pubmed ID: 30046032

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