Focused ultrasound mitigates pathology and improves spatial memory in Alzheimer's mice and patients
Maria Eleni Karakatsani, Robin Ji, Maria F. Murillo, Tara Kugelman, Nancy Kwon, Yeh‐Hsing Lao, Keyu Liu, Antonios N. Pouliopoulos, Lawrence S. Honig, Karen Duff, Elisa E. Konofagou
Abstract
For the first time, it is shown that bilateral FUS-induced BBB opening significantly and simultaneously ameliorates both coexistent pathologies, which translated to improvements in spatial memory of transgenic animals with complex AD, the human mimicking phenotype. The level of cognitive improvement was significantly correlated with the volume of BBB opening. Non-transgenic animals were also shown to exhibit similar memory amelioration for the first time, indicating that BBB opening results into benefits in the neuronal function regardless of the existence of AD pathology. A potential mechanism of action for the reduction of the both pathologies investigated was the cholesterol metabolism, specifically the LRP1b receptor, which exhibited increased expression levels in transgenic mice following FUS-induced BBB opening. Initial clinical evidence supported that the beta amyloid reduction shown in rodents could be translatable to humans with significant amyloid reduction shown in the treated hemisphere.