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Jürgen Götz
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Balbi, M.;  Blackmore, D.G.;  Padmanabhan, P.;  Götz, J. Ultrasound in Senescent Mice and Alzheimer’s Mouse Models. Encyclopedia. Available online: https://encyclopedia.pub/entry/24320 (accessed on 04 July 2024).
Balbi M,  Blackmore DG,  Padmanabhan P,  Götz J. Ultrasound in Senescent Mice and Alzheimer’s Mouse Models. Encyclopedia. Available at: https://encyclopedia.pub/entry/24320. Accessed July 04, 2024.
Balbi, Matilde, Daniel G. Blackmore, Pranesh Padmanabhan, Jürgen Götz. "Ultrasound in Senescent Mice and Alzheimer’s Mouse Models" Encyclopedia, https://encyclopedia.pub/entry/24320 (accessed July 04, 2024).
Balbi, M.,  Blackmore, D.G.,  Padmanabhan, P., & Götz, J. (2022, June 22). Ultrasound in Senescent Mice and Alzheimer’s Mouse Models. In Encyclopedia. https://encyclopedia.pub/entry/24320
Balbi, Matilde, et al. "Ultrasound in Senescent Mice and Alzheimer’s Mouse Models." Encyclopedia. Web. 22 June, 2022.
Ultrasound in Senescent Mice and Alzheimer’s Mouse Models
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This entry is adapted from the peer-reviewed paper 10.3390/brainsci12060775

Ultrasound is routinely used for a wide range of diagnostic imaging applications. However, given that ultrasound can operate over a wide range of parameters that can all be modulated, its applicability extends far beyond the bioimaging field. In fact, the modality has emerged as a hybrid technology that effectively assists drug delivery by transiently opening the blood–brain barrier (BBB) when combined with intravenously injected microbubbles, and facilitates neuromodulation. Studies in aged mice contributed to an insight into how low-intensity ultrasound brings about its neuromodulatory effects, including increased synaptic plasticity and improved cognitive functions, with a potential role for neurogenesis and the modulation of NMDA receptor-mediated neuronal signalling. The currently available ultrasound approaches and how studies in senescent mice are relevant for AD and can accelerate the application of low-intensity ultrasound in the clinic are discussed.

amyloid long-term potentiation low-intensity ultrasound mechanosensory receptor neurogenesis neuromodulation NMDA receptor (NR) senescence Tau

1. Introduction to Therapeutic Ultrasound

US is a mechanical pressure wave (sound) at a frequency above the range of human hearing (>20 kHz), and it is used routinely in the MHz range for diagnostic imaging applications. For therapeutic purposes, US is applied to the human brain at much lower frequencies (typically <500 kHz) than for imaging purposes aimed at, e.g., peripheral soft tissue such as the womb. This is because high-frequency US is attenuated by the human (and less so by the mouse) skull. When delivered through a single curved transducer (or an array composed of either flat or curved transducers), the ultrasound energy can be most effectively focused on the target within the brain tissue (FUS). Of note, therapeutic US possesses numerous advantages over more traditional approaches. For example, unlike conventional drug treatment, directing the US beam exclusively to distinct brain areas, such as the hippocampus, allows for both region-specific and brain-wide treatment. The former is critical for more confined diseases, such as Parkinson’s disease, with spatially restricted pathology, and the latter, researchers would argue, for diseases with a more diffuse and wide-spread pathology such as AD. In addition, in contrast to radiation therapy, US exerts its effects only in the focal zone and not in the tissue through which the sound waves travel, thereby enhancing its safety profile.
The FDA has approved high frequency US applied as a continuous (i.e., unpulsed) waveform to coagulate (ablate) thalamic tissue (thalamotomy), for the treatment of essential tremor (ET) and tremor-dominant Parkinson’s disease (TDPD) [1][2]. Other FUS mechanisms under active investigation, several in the context of brain tumours, are hyperthermia (to induce uptake of chemotherapeutics and immunogenicity [3]), sonodynamic therapy (using US to generate reactive oxygen species from sonosensitisers [4]), histotripsy (to liquefy blood clots), and sonothrombolysis (to remove blood clots in stroke patients [5][6]), as recently discussed in detail in an excellent review [7].
By using pulsed waveforms at low sub-MHz frequencies, US has further been explored as a non-invasive tool to either open the BBB and/or induce neuromodulatory effects. This division is in some respect operational because in order to induce BBB opening with US, this does not necessarily exclude US also exerting neuromodulatory effects. Researchers refer the reader to several excellent reviews that are available in the neuromodulatory space using US [8][9][10][11][12].

2. Applications of Low-Frequency Ultrasound to Alzheimer’s Mouse Models

In this section, researchers discuss the application of US to AD mouse models. Histopathologically, AD is characterised by extracellular Aβ deposits (senile plaques), intraneuronal Tau aggregates (neurofibrillary tangles and neuropil threads), as well as neuroinflammation [13]. The currently available AD therapies (except for the recently approved—and highly disputed—anti-Aβ antibody aducanumab) do not delay the neurodegenerative process and only provide symptomatic relief. Approved AD drugs are the acetylcholine esterase inhibitors donepezil (Aricept), rivastigmine (Exelon) and galantamine (Razadyne), and the NMDA receptor antagonist memantine (Namenda). The mainstay of the clinical trials that have been performed over the recent years are vaccines targeting Aβ and Tau, based on the assumption that these two molecules, which form insoluble toxic protein aggregates that constitute the hallmark lesions of AD, both initiate and drive the disease. The leading hypothesis in the field is the amyloid cascade hypothesis that places Aβ upstream of Tau [14]; however, there is also a crucial role for Tau given that Aβ toxicity is Tau-dependent, as formulated in the Tau axis hypothesis [15][16]. In transgenic animal models with either Aβ or Tau pathology, transgenic expression of mutant forms of the genes encoding APP (from which Aβ is derived by proteolytic cleavage) and Tau leads to the formation of pathological aggregates and ensuing cognitive impairments, and removing these aggregates restores cognitive functions [17].
Regarding protein aggregates, there are two fundamental treatment options, either preventing their formation in the first place or when they have formed removing them. It seemed therefore reasonable to trial the US technology and attempt to clear Aβ and Tau aggregates and thereby restore cognitive functions. It came as a surprise that Aβ could be significantly cleared by using US+MB without a therapeutic agent [18][19]. By using US in a scanning mode (SUS) and 5–8 weekly treatment sessions, not only was Aβ effectively cleared, but memory functions were also improved or even restored as shown in three complementary behavioural tests, the Y-maze, novel objection recognition, and active place avoidance tests [19]. Aβ clearance by dormant microglia was identified as an underlying therapeutic mechanism. The microglia had taken up Aβ into their lysosomes, a process potentially mediated by unknown blood-borne factors that had entered the brain in response to US+MB-mediated BBB opening [18][19]. In a recent RNAseq transcriptomic analysis of microglia isolated from US+MB-treated APP23 mice followed by incubation with the amyloid dye methoxy-XO4, ‘cell cycle’ and ‘phagocytosis’ genes were specifically activated, hinting at the underlying microglial activation mechanism [20] (see also a recent study aggregating 75 murine transcriptomes in response to US+MB [21]). Importantly, US+MB was even shown to be safe in aged APP23 mice that display pronounced cerebral amyloid angiopathy (CAA). Again, Aβ was found to be cleared effectively by microglia and while not reducing the total plaque area, US+MB reduced the fraction of large plaques. An obvious question is whether the clearance effects are long-lasting. Poon and colleagues performed a time-course experiment using two-photon microscopy to examine this. The study revealed that one single US+MB session (dose) reduced the size of plaques for two weeks, advocating fortnightly treatment sessions in human AD [22] (for comparison, vaccinations are often spaced out by four weeks). Longer time frames have not been investigated [22]. The team also performed two-photon microscopy to assess leukocyte infiltration in response to US+MB treatment and found significantly more neutrophils in the sonicated compared to the contralateral hemisphere, suggesting a role not only for brain-resident microglia but also peripheral neutrophils, the first line of defence of the innate immune system [23]. Of note, US+MB has assisted the delivery of other agents, including the GSK inhibitor AR-A014418 [24], a TrkA agonist [25], and exosomes [26] in Aβ-depositing mice, and Aβ-targeting metal complexes in wild-type mice [27]. More recently, stem cells have been delivered together with anti-Aβ antibodies [28]. Of note, while in APP23 mice it has been shown that BBB opening is required to clear Aβ [29], USonly applied in another AD mouse model (using a transducer at a higher (1.875 MHz) frequency) activated endothelial nitric oxide synthase (eNOS), an enzyme with a role in angiogenesis and vasodilation, stimulated microglia and removed Aβ [30]. In the same publication, USonly-induced cognitive improvements in a model of vascular dementia were found to be abrogated on an eNOS knockout background [30].
US+MB has also been applied to Tau transgenic mouse models. Tau is a much harder target than Aβ, given that its pathology is largely intracellular and therefore less accessible to therapeutic agents. In Tau transgenic pR5 mice (that carry the P301L mutation found in frontotemporal dementia), US+MB (which constituted one of four treatment arms) reduced Tau pathology as shown for the amygdala [31]. Reduced Tau pathology was also reported in another Tau transgenic mouse model, rTg4510, using unilateral US+MB treatments [32]. In Tau transgenic K3 mice (carrying the frontotemporal dementia mutation K369I) with a memory and motor deficit, US+MB was shown to partly ameliorate these behavioural phenotypes, and Tau was cleared by the activation of neuronal autophagy (rather than microglial activation) [33]. Given that Tau is a protein that has been demonstrated to be degraded in lysosomes via autophagy [34], US+MB therefore appears to boost an intrinsic mechanism that neurons use to clear Tau. Finally, US+MB has also been applied to a mouse model with both Aβ and Tau pathology in the 3xTg-AD strain (although in these mice the Tau pathology is very modest) [35]. The study confirmed microglial engulfment of amyloid and improvements in learning and memory. Moreover, a proteomic analysis was performed to gain additional insight into potential mechanisms.
US+MB has further been combined with anti-Tau and anti-Aβ antibodies, exploring antibody formats ranging from single-chain variable fragments (ScFvs) with a molecular weight of 29 kDa to full-sized immunoglobulins with a molecular weight of 150 kDa. Nisbet and colleagues explored US+MB together with an ScFv antibody fragment targeting 2N Tau (RN2N), with the epitope being present in 2N4R Tau isoform over-expressing pR5 mice [31]. The study found that the combination treatment was superior to the single treatment arms of either using US+MB or the RN2N ScFv alone. Interestingly, in the combination treatment arm, the antibody fragment was not only shown to be taken up by the brain, but also to effectively distribute into neuronal cell bodies and dendrites, demonstrating that US+MB not only overcomes the BBB but also the plasma membrane as the second barrier [31]. In a follow-up study, different RN2N antibody formats were explored (ScFv, Fab and IgG), revealing an up to 30-fold increased uptake of the therapeutic antibody mediated by US+MB+mAb [36].
Jordao and colleagues evaluated the anti-Aβ antibody BAM-10 and showed US+MB-mediated Aβ reductions in the TgCRND8 mouse model [37]. The clinically approved anti-Aβ antibody aducanumab has been tested in APP23 mice in a combination trial, revealing improved cognitive outcomes compared to the single treatment arms of either antibody alone or US+MB alone [38]. A similar approach was pursued by Lemere and colleagues, who delivered an anti-pyroglutamylated Aβ antibody to aged APP/PS1dE9 mice [39]. They showed that mice administered with the combination treatment had reduced hippocampal plaque burden compared to controls. In contrast, in the aducanumab study, all three treatment arms (antibody alone, US+MB alone, and the combination treatment US+MB+mAb) reduced plaque burden in the hippocampus, whereas in the cortex, only the combination treatment was effective [38]. It was argued that hippocampal plaques develop later than cortical plaques, and that the differences observed in clearance for the two brain areas could be related to the timing of the treatments.
Collectively, these promising preclinical data have spurred several small cohort clinical trials that have shown safety and feasibility of US+MB-mediated BBB opening in AD (NCT04118764, NCT04526262, NCT03119961, NCT03739905, NCT03671889, and NCT02986932). The trials differ in that they either use the MRI-guided ExAblate Neuro system multi-element array operated at 220 kHz (Insightec) [40][41], a 1 MHz transducer implanted in the skull bone thickness and connected to an external power supply via a transdermal needle connection during activation and facing the brain (Carthera: Sonocloud [42]), or a single 0.25 MHz element transducer with guidance provided by the Brainsight neuronavigation system (Columbia University) as outlined in a macaque study [43]. Whether US+MB-medicated BBB opening will achieve statistically significant Aβ reductions and cognitive improvements in human patients, and whether these improvements are long-lasting, needs to be determined. In support of combining US+MB with an anti-Aβ antibody, in a recent article, Karran and De Strooper argue that ‘the speed of amyloid removal from the brain by a potential therapy will be important in demonstrating clinical benefit in the context of a clinical trial’ [44], clearly making a case for US+MB-mediated enhanced delivery of antibodies such as aducanumab into the brain of AD patients.

References

  1. Elias, W.J.; Lipsman, N.; Ondo, W.G.; Ghanouni, P.; Kim, Y.G.; Lee, W.; Schwartz, M.; Hynynen, K.; Lozano, A.M.; Shah, B.B.; et al. A Randomized Trial of Focused Ultrasound Thalamotomy for Essential Tremor. N. Engl. J. Med. 2016, 375, 730–739.
  2. Sinai, A.; Nassar, M.; Sprecher, E.; Constantinescu, M.; Zaaroor, M.; Schlesinger, I. Focused Ultrasound Thalamotomy in Tremor Dominant Parkinson’s Disease: Long-Term Results. J. Parkinson’s Dis. 2022, 12, 199–206.
  3. Cohen-Inbar, O.; Xu, Z.; Sheehan, J.P. Focused ultrasound-aided immunomodulation in glioblastoma multiforme: A therapeutic concept. J. Ther. Ultrasound 2016, 4, 2.
  4. Yoshida, M.; Kobayashi, H.; Terasaka, S.; Endo, S.; Yamaguchi, S.; Motegi, H.; Itay, R.; Suzuki, S.; Brokman, O.; Shapira, Y.; et al. Sonodynamic Therapy for Malignant Glioma Using 220-kHz Transcranial Magnetic Resonance Imaging-Guided Focused Ultrasound and 5-Aminolevulinic acid. Ultrasound Med. Biol. 2019, 45, 526–538.
  5. Baron, C.; Aubry, J.F.; Tanter, M.; Meairs, S.; Fink, M. Simulation of intracranial acoustic fields in clinical trials of sonothrombolysis. Ultrasound Med. Biol. 2009, 35, 1148–1158.
  6. Alexandrov, A.V.; Kohrmann, M.; Soinne, L.; Tsivgoulis, G.; Barreto, A.D.; Demchuk, A.M.; Sharma, V.K.; Mikulik, R.; Muir, K.W.; Brandt, G.; et al. Safety and efficacy of sonothrombolysis for acute ischaemic stroke: A multicentre, double-blind, phase 3, randomised controlled trial. Lancet Neurol. 2019, 18, 338–347.
  7. Meng, Y.; Hynynen, K.; Lipsman, N. Applications of focused ultrasound in the brain: From thermoablation to drug delivery. Nat. Rev. Neurol. 2021, 17, 7–22.
  8. Naor, O.; Krupa, S.; Shoham, S. Ultrasonic neuromodulation. J. Neural Eng. 2016, 13, 031003.
  9. Tyler, W.J.; Lani, S.W.; Hwang, G.M. Ultrasonic modulation of neural circuit activity. Curr. Opin. Neurobiol. 2018, 50, 222–231.
  10. Munoz, F.; Aurup, C.; Konofagou, E.E.; Ferrera, V.P. Modulation of Brain Function and Behavior by Focused Ultrasound. Curr. Behav. Neurosci. Rep. 2018, 5, 153–164.
  11. Blackmore, J.; Shrivastava, S.; Sallet, J.; Butler, C.R.; Cleveland, R.O. Ultrasound Neuromodulation: A Review of Results, Mechanisms and Safety. Ultrasound Med. Biol. 2019, 45, 1509–1536.
  12. Rabut, C.; Yoo, S.; Hurt, R.C.; Jin, Z.; Li, H.; Guo, H.; Ling, B.; Shapiro, M.G. Ultrasound Technologies for Imaging and Modulating Neural Activity. Neuron 2020, 108, 93–110.
  13. Goedert, M.; Spillantini, M.G. A century of Alzheimer’s disease. Science 2006, 314, 777–781.
  14. Hardy, J. Alzheimer’s disease: The amyloid cascade hypothesis: An update and reappraisal. J. Alzheimers Dis. 2006, 9, 151–153.
  15. Ittner, L.M.; Ke, Y.D.; Delerue, F.; Bi, M.; Gladbach, A.; van Eersel, J.; Wolfing, H.; Chieng, B.C.; Christie, M.J.; Napier, I.A.; et al. Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer’s disease mouse models. Cell 2010, 142, 387–397.
  16. Ittner, L.M.; Götz, J. Amyloid-beta and tau—A toxic pas de deux in Alzheimer’s disease. Nat. Rev. Neurosci. 2011, 12, 65–72.
  17. Götz, J.; Bodea, L.G.; Goedert, M. Rodent models for Alzheimer disease. Nat. Rev. Neurosci. 2018, 19, 583–598.
  18. Jordao, J.F.; Thevenot, E.; Markham-Coultes, K.; Scarcelli, T.; Weng, Y.Q.; Xhima, K.; O’Reilly, M.; Huang, Y.; McLaurin, J.; Hynynen, K.; et al. Amyloid-beta plaque reduction, endogenous antibody delivery and glial activation by brain-targeted, transcranial focused ultrasound. Exp. Neurol. 2013, 248, 16–29.
  19. Leinenga, G.; Götz, J. Scanning ultrasound removes amyloid-beta and restores memory in an Alzheimer’s disease mouse model. Sci. Transl. Med. 2015, 7, 278ra233.
  20. Leinenga, G.; Bodea, L.G.; Schröder, J.; Sun, G.; Zhou, Y.; Song, J.; Grubman, A.; Polo, J.M.; Götz, J. Transcriptional signature in microglia isolated from an Alzheimer’s disease mouse model treated with scanning ultrasound. Bioeng. Transl. Med. 2021.
  21. Mathew, A.S.; Gorick, C.M.; Price, R.J. Multiple regression analysis of a comprehensive transcriptomic data assembly elucidates mechanically- and biochemically-driven responses to focused ultrasound blood-brain barrier disruption. Theranostics 2021, 11, 9847–9858.
  22. Poon, C.T.; Shah, K.; Lin, C.; Tse, R.; Kim, K.K.; Mooney, S.; Aubert, I.; Stefanovic, B.; Hynynen, K. Time course of focused ultrasound effects on beta-amyloid plaque pathology in the TgCRND8 mouse model of Alzheimer’s disease. Sci. Rep. 2018, 8, 14061.
  23. Poon, C.; Pellow, C.; Hynynen, K. Neutrophil recruitment and leukocyte response following focused ultrasound and microbubble mediated blood-brain barrier treatments. Theranostics 2021, 11, 1655–1671.
  24. Hsu, P.H.; Lin, Y.T.; Chung, Y.H.; Lin, K.J.; Yang, L.Y.; Yen, T.C.; Liu, H.L. Focused Ultrasound-Induced Blood-Brain Barrier Opening Enhances GSK-3 Inhibitor Delivery for Amyloid-Beta Plaque Reduction. Sci. Rep. 2018, 8, 12882.
  25. Xhima, K.; Markham-Coultes, K.; Kofoed, R.H.; Saragovi, H.U.; Hynynen, K.; Aubert, I. Ultrasound delivery of a TrkA agonist confers neuroprotection to Alzheimer-associated pathologies. Brain 2021, awab460.
  26. Deng, Z.; Wang, J.; Xiao, Y.; Li, F.; Niu, L.; Liu, X.; Meng, L.; Zheng, H. Ultrasound-mediated augmented exosome release from astrocytes alleviates amyloid-beta-induced neurotoxicity. Theranostics 2021, 11, 4351–4362.
  27. Chan, T.G.; Ruehl, C.L.; Morse, S.V.; Simon, M.; Rakers, V.; Watts, H.; Aprile, F.A.; Choi, J.J.; Vilar, R. Modulation of amyloid-beta aggregation by metal complexes with a dual binding mode and their delivery across the blood-brain barrier using focused ultrasound. Chem. Sci. 2021, 12, 9485–9493.
  28. Zhu, Q.; Xu, X.; Chen, B.; Liao, Y.; Guan, X.; He, Y.; Cui, H.; Rong, Y.; Liu, Z.; Xu, Y. Ultrasound-targeted microbubbles destruction assists dual delivery of beta-amyloid antibody and neural stem cells to restore neural function in transgenic mice of Alzheimer’s disease. Med. Phys. 2022, 49, 1357–1367.
  29. Leinenga, G.; Koh, W.K.; Götz, J. Scanning ultrasound in the absence of blood-brain barrier opening is not sufficient to clear beta-amyloid plaques in the APP23 mouse model of Alzheimer’s disease. Brain Res. Bull. 2019, 153, 8–14.
  30. Eguchi, K.; Shindo, T.; Ito, K.; Ogata, T.; Kurosawa, R.; Kagaya, Y.; Monma, Y.; Ichijo, S.; Kasukabe, S.; Miyata, S.; et al. Whole-brain low-intensity pulsed ultrasound therapy markedly improves cognitive dysfunctions in mouse models of dementia—Crucial roles of endothelial nitric oxide synthase. Brain Stimul. 2018, 11, 959–973.
  31. Nisbet, R.M.; van der Jeugd, A.; Leinenga, G.; Evans, H.T.; Janowicz, P.W.; Götz, J. Combined effects of scanning ultrasound and a tau-specific single chain antibody in a tau transgenic mouse model. Brain 2017, 140, 1220–1230.
  32. Karakatsani, M.E.; Kugelman, T.; Ji, R.; Murillo, M.; Wang, S.; Niimi, Y.; Small, S.A.; Duff, K.E.; Konofagou, E.E. Unilateral Focused Ultrasound-Induced Blood-Brain Barrier Opening Reduces Phosphorylated Tau from The rTg4510 Mouse Model. Theranostics 2019, 9, 5396–5411.
  33. Pandit, R.; Leinenga, G.; Götz, J. Repeated ultrasound treatment of tau transgenic mice clears neuronal tau by autophagy and improves behavioral functions. Theranostics 2019, 9, 3754–3767.
  34. Caballero, B.; Wang, Y.; Diaz, A.; Tasset, I.; Juste, Y.R.; Stiller, B.; Mandelkow, E.M.; Mandelkow, E.; Cuervo, A.M. Interplay of pathogenic forms of human tau with different autophagic pathways. Aging Cell 2018, 17, e12692.
  35. Shen, Y.; Hua, L.; Yeh, C.K.; Shen, L.; Ying, M.; Zhang, Z.; Liu, G.; Li, S.; Chen, S.; Chen, X.; et al. Ultrasound with microbubbles improves memory, ameliorates pathology and modulates hippocampal proteomic changes in a triple transgenic mouse model of Alzheimer’s disease. Theranostics 2020, 10, 11794–11819.
  36. Janowicz, P.W.; Leinenga, G.; Götz, J.; Nisbet, R.M. Ultrasound-mediated blood-brain barrier opening enhances delivery of therapeutically relevant formats of a tau-specific antibody. Sci. Rep. 2019, 9, 9255.
  37. Jordao, J.F.; Ayala-Grosso, C.A.; Markham, K.; Huang, Y.; Chopra, R.; McLaurin, J.; Hynynen, K.; Aubert, I. Antibodies targeted to the brain with image-guided focused ultrasound reduces amyloid-beta plaque load in the TgCRND8 mouse model of Alzheimer’s disease. PLoS ONE 2010, 5, e10549.
  38. Leinenga, G.; Koh, W.K.; Götz, J. A comparative study of the effects of Aducanumab and scanning ultrasound on amyloid plaques and behavior in the APP23 mouse model of Alzheimer disease. Alzheimers Res. Ther. 2021, 13, 76.
  39. Sun, T.; Shi, Q.; Zhang, Y.; Power, C.; Hoesch, C.; Antonelli, S.; Schroeder, M.K.; Caldarone, B.J.; Taudte, N.; Schenk, M.; et al. Focused ultrasound with anti-pGlu3 Abeta enhances efficacy in Alzheimer’s disease-like mice via recruitment of peripheral immune cells. J. Control. Release 2021, 336, 443–456.
  40. Lipsman, N.; Meng, Y.; Bethune, A.J.; Huang, Y.; Lam, B.; Masellis, M.; Herrmann, N.; Heyn, C.; Aubert, I.; Boutet, A.; et al. Blood-brain barrier opening in Alzheimer’s disease using MR-guided focused ultrasound. Nat. Commun. 2018, 9, 2336.
  41. Park, S.H.; Baik, K.; Jeon, S.; Chang, W.S.; Ye, B.S.; Chang, J.W. Extensive frontal focused ultrasound mediated blood-brain barrier opening for the treatment of Alzheimer’s disease: A proof-of-concept study. Transl. Neurodegener. 2021, 10, 44.
  42. Epelbaum, S.; Burgos, N.; Canney, M.; Matthews, D.; Houot, M.; Santin, M.D.; Desseaux, C.; Bouchoux, G.; Stroer, S.; Martin, C.; et al. Pilot study of repeated blood-brain barrier disruption in patients with mild Alzheimer’s disease with an implantable ultrasound device. Alzheimers Res. Ther. 2022, 14, 40.
  43. Pouliopoulos, A.N.; Wu, S.Y.; Burgess, M.T.; Karakatsani, M.E.; Kamimura, H.A.S.; Konofagou, E.E. A Clinical System for Non-invasive Blood-Brain Barrier Opening Using a Neuronavigation-Guided Single-Element Focused Ultrasound Transducer. Ultrasound Med. Biol. 2020, 46, 73–89.
  44. Karran, E.; De Strooper, B. The amyloid hypothesis in Alzheimer disease: New insights from new therapeutics. Nat. Rev. Drug Discov. 2022, 21, 306–318.
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Subjects: Neurosciences
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Matilde Balbi
,
Daniel G. Blackmore
,
Pranesh Padmanabhan
,
Jürgen Götz
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Update Date: 22 Jun 2022
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