Effects of blood-brain barrier opening using ultrasound on tauopathies: A systematic review

Blood-brain barrier opening with ultrasound can potentiate drug efficacy in the treatment of brain pathologies and also provides therapeutic effects on its own. It is an innovative tool to transiently, repeatedly and safely open the barrier, with studies showing beneficial effects in both preclinical models for Alzheimer's disease and recent clinical studies. The first preclinical and clinical work has mainly shown a decrease in amyloid burden in mice models and in patients. However, Alzheimer's disease pathology also encompasses tauopathy, which is closely related to cognitive decline, making it a crucial therapeutic target. The effects of blood-brain barrier opening with ultrasound have been rarely assessed on tau and are still unclear. Methods: This systematic review, conducted through searches using Pubmed, Embase, Web of Science and Cochrane Central databases, extracted results of 15 studies reporting effects of blood-brain barrier opening using ultrasound on tau proteins. Results: This review of the literature indicates that blood-brain barrier opening using ultrasound can decrease the extent of the tau pathology or potentialize the effect of a therapeutic drug. However, selected studies report paradoxically that blood-brain barrier opening can increase tau pathology burden and induce brain damage. Discussion: Apparent discrepancies between reports could originate from the variability in protocols or analytical methods that may impact the effects of blood-brain barrier opening with ultrasound on tauopathies, glial populations, tissue integrity and functional outcomes. Conclusion: This calls for a better standardization effort combined with improved methodologies allowing between-studies comparisons, and for further understanding of the effects of blood-brain barrier opening on tau pathology as an essential prerequisite before translation to clinic.