Time course of focused ultrasound effects on β-amyloid plaque pathology in the TgCRND8 mouse model of Alzheimer's disease

Scientific Reports
Charissa T PoonKullervo Hynynen

Abstract

Previous studies have demonstrated that temporarily increasing the permeability of the blood-brain barrier using focused ultrasound can reduce β-amyloid plaque load and improve cognitive function in animal models of Alzheimer's disease. However, the underlying mechanism and duration for which the effects of one treatment persists for are unknown. Here, we used in vivo two-photon fluorescence microscopy to track changes in β-amyloid plaque sizes in the TgCRND8 mouse model of Alzheimer's disease after one focused ultrasound treatment. We found that one treatment reduced plaques to 62 ± 16% (p ≤ 0.001) of their original volume two days post-sonication; this decrease in size persisted for two weeks. We then sought to evaluate the effectiveness of biweekly focused ultrasound treatments using magnetic resonance imaging-guided focused ultrasound treatments. Three to five biweekly treatments resulted in a 27 ± 7% (p ≤ 0.01) decrease in plaque number and 40 ± 10% (p ≤ 0.01) decrease in plaque surface area compared to untreated littermates. This study demonstrates that one focused ultrasound treatment reduces the size of existing β-amyloid plaques for two weeks, and that repeated biweekly focused ultrasound treatments is an effective met...Continue Reading

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Citations

Jul 22, 2019·Journal of Controlled Release : Official Journal of the Controlled Release Society·Ying MengNir Lipsman
Oct 28, 2020·Nature Reviews. Neurology·Ying MengNir Lipsman
Mar 14, 2020·Ultrasound in Medicine & Biology·Klazina KooimanChristy K Holland
Apr 29, 2021·Proceedings of the National Academy of Sciences of the United States of America·Scott R BurksJoseph A Frank
Jun 14, 2021·Advances in Colloid and Interface Science·Marie Pierre Krafft, Jean G Riess
Mar 24, 2021·Annual Review of Biomedical Engineering·Dallan McMahonKullervo Hynynen
Sep 24, 2021·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Si ChenHong Chen
Sep 26, 2021·Translational Neurodegeneration·Francisca MonteiroFilipe S Silva

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Methods Mentioned

BETA
fluorescence microscopy
fluorescence
transgenic

Software Mentioned

MATLAB
GraphPad
StereoInvestigator
GraphPad Prism Prism
MATLAB and Statistics Toolbox

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