Safety and Efficacy of Scanning Ultrasound Treatment of Aged APP23 Mice

Frontiers in Neuroscience
Gerhard Leinenga, Jürgen Götz

Abstract

Deposition of amyloid-β (Aβ) peptide leads to amyloid plaques that together with tau deposits characterize the brains of patients with Alzheimer's disease (AD). In modeling this pathology, transgenic animals such as the APP23 strain, that expresses a mutant form of the amyloid precursor protein found in familial cases of AD, have been instrumental. In previous studies, we have shown that repeated treatments with ultrasound in a scanning mode (termed scanning ultrasound or SUS) were effective in removing Aβ and restoring memory functions, without the need for a therapeutic agent such as an Aβ antibody. Considering that age is the most important risk factor for AD, we extended this study in which the mice were only 12 months old at the time of treatment by assessing a cohort of 2 year-old mice. Interestingly, at this age, APP23 mice are characterized by cerebral amyloid angiopathy (CAA) and the presence of occasional microbleeds. We found that SUS in aged mice that have been exposed to four SUS sessions that were spread out over 8 weeks and analyzed 4 weeks later did not show evidence of increased CAA or microbleeds. Furthermore, amyloid was reduced as assessed by methoxy-XO4 fluorescence. In addition, plaque-associated microglia...Continue Reading

References

Dec 16, 1997·Proceedings of the National Academy of Sciences of the United States of America·C Sturchler-PierratB Sommer
Nov 26, 1999·Proceedings of the National Academy of Sciences of the United States of America·M E CalhounM Jucker
Sep 17, 2002·Journal of Neuropathology and Experimental Neurology·William E KlunkBradley T Hyman
May 11, 2006·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Scott B RaymondBrian J Bacskai
Oct 28, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yona LevitesTodd E Golde
Aug 4, 2007·The Journal of the Acoustical Society of America·Charles F CaskeyKatherine W Ferrara
Aug 22, 2009·IEEE Transactions on Bio-medical Engineering·Ralf SeipKlaus Tiemann
Jun 25, 2010·Bubble Science Engineering and Technology·Shashank Sirsi, Mark Borden
Dec 8, 2010·Acta Neuropathologica·Steffen BurgoldJochen Herms
Oct 25, 2011·Neurobiology of Aging·Nivetha MurugesanJoel S Pachter
Feb 11, 2012·Journal of Neurology·Ronit GiladMordechai Loyberboim
Aug 30, 2012·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·William M Pardridge
Feb 6, 2013·Theranostics·Elisa E Konofagou
Sep 7, 2013·Frontiers in Neuroengineering·Andrew D WongPeter C Searson
Aug 12, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Alison BurgessKullervo Hynynen
Mar 13, 2015·Science Translational Medicine·Gerhard Leinenga, Jürgen Götz
Feb 20, 2016·Nature Reviews. Neurology·Gerhard LeinengaJürgen Götz
Sep 2, 2016·Nature·Jeff SevignyAlfred Sandrock
Jul 15, 2017·Stroke; a Journal of Cerebral Circulation·Marilena MarinescuRoland Veltkamp
Aug 28, 2017·Journal of Neurology, Neurosurgery, and Psychiatry·Gargi BanerjeeDavid J Werring
Sep 19, 2017·The Medical Journal of Australia·Gerhard LeinengaJürgen Götz
Oct 7, 2017·Nature Reviews. Drug Discovery·Chuanzhou Li, Jürgen Götz

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Citations

May 13, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Stephan SchillingCynthia A Lemere
Dec 9, 2020·Proceedings of the National Academy of Sciences of the United States of America·Sonam DubeyIsabelle Aubert
Dec 4, 2019·Advanced Drug Delivery Reviews·Rucha PanditJürgen Götz
Oct 28, 2020·Nature Reviews. Neurology·Ying MengNir Lipsman
Jun 1, 2021·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Claire E SextonMaria C Carrillo
Jun 30, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Tao SunCynthia A Lemere
Mar 24, 2021·Annual Review of Biomedical Engineering·Dallan McMahonKullervo Hynynen
Sep 26, 2021·Translational Neurodegeneration·Francisca MonteiroFilipe S Silva

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Methods Mentioned

BETA
transgenic
electron tomography

Clinical Trials Mentioned

NCT02986932
NCT03119961

Software Mentioned

GraphPad
Prism
Nikon NIS
ImageJ

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