OO023 - TOWARDS A MECHANISTIC UNDERSTANDING OF THERAPEUTIC ULTRASOUND AS A TREATMENT MODALITY FOR ALZHEIMER DISEASE (ID 384)
Abstract
Aims
Therapeutic ultrasound is an emerging therapeutic modality that can be used in a scanning mode in combination with intravenously injected microbubbles to achieve transient blood-brain barrier (BBB) opening (SUS+MB) for the delivery of therapeutic agents, or without microbubbles as a neuromodulatory tool (SUSonly). Given that both physiological and pathological ageing (Alzheimer’s disease) lead to a progressive cognitive decline (Götz et al., NatRevNeurosci 2018), the question arises what the therapeutic effects are in Alzheimer’s mouse models and senescent mice and whether the findings can be translated into clinical practice.
Methods
We explored the two ultrasound strategies over a range of ultrasound parameters in amyloid-depositing APP23 mice and senescent wild-type mice, with up to six weekly treatment sessions. Analysis tools included an extensive behavioural, electrophysiological, biochemical, histological, proteomics and imaging analysis.
Results
We will discuss data that reveal that SUS+MB reduces amyloid pathology and restores cognition (Leinenga & Götz, ScienceTranslMed 2015), that BBB opening is required for amyloid clearance (Leinenga et al., BrainResBull 2019) and whether SUSonly is sufficient to restore cognition (in progress). We will further discuss published work (Blackmore et al., MolPsych 2021) and follow-up studies that reveal that both SUS+MB and SUSonly restore LTP deficits and improve cognition in senescent mice via pleiotropic mechanisms including NMDAR-dependent signalling. We will further discuss the development of a clinical-trial ready device as part of setting up a therapeutic ultrasound platform.
Conclusions
We conclude that therapeutic ultrasound is a non-invasive modality for the treatment for Alzheimer’s disease and other brain diseases.
