Ultrasound blood–brain barrier opening: A new era of treatment for Alzheimer's disease?

The application of FUS spans various domains, encompassing imaging, tumor ablation, neuromodulation, targeted gene therapy, and increasing drug delivery to the cerebral region.1 Magnetic resonance imaging (MRI) guided FUS uses focused ultrasound energy, delivered transcranially, to treat a variety of neurological diseases, such as essential tremor (ET), Parkinson disease (PD), neuropathic pain, and dystonia.6,7 A variety of neuropathic pain syndromes have been successfully treated using MRI-guided FUS central lateral thalamotomy.6 MRI-guided FUS ventralis intermedius (VIM) thalamotomy is now a well-established and federal drug administration (FDA) approved therapy in medication-refractory ET and for the motor symptoms of PD. The use of concurrent MRI allows highly accurate spatial and thermal guidance, with fine anatomical detail, high soft-tissue contrast, and real-time monitoring of the treatment zone. Currently, there are approximately 46 million people living with AD worldwide, and the number is expected to triple by 2050, posing a huge challenge for health care.8 At present, the recognized pathological mechanism of AD is the amyloid cascade theory, characterized by the accumulation of amyloid-beta (Aβ) protein, which leads to senile plaques and neurofibrillary tangles within neurons. Using less than 1% of the energy required for ablation, the BBB along the frontal white matter was successfully confirmed, and the target area was enhanced by local gadolinium extravasation, which proved to be reproducible, with no serious adverse effects.13 Another study aimed to evaluate the efficacy and safety of MRI-guided FUS in PD via a systematic review and meta- analysis of 20 studies involving 258 patients from 2014 to 2023, which showed that MRI-guided FUS provided an effective and relatively safe treatment option for patients with drug-resistant PD-related tremor.14 Therefore, MRI-guided FUS can safely and reversibly breach the BBB without causing severe adverse events. CONFLICT OF INTEREST STATEMENT The authors have no conflicts of interest to disclose.