Ultrasound Blood-Brain Barrier Opening and Aducanumab in Alzheimer's Disease

Ali R Rezai; Pierre-Francois D'Haese; Victor Finomore; Jeffrey Carpenter; Manish Ranjan; Kirk Wilhelmsen; Rashi I Mehta; Peng Wang; Umer Najib; Camila Vieira Ligo Teixeira; Tasneem Arsiwala; Abdul Tarabishy; Padmashree Tirumalai; Daniel O Claassen; Sally Hodder; Marc W Haut

doi:10.1056/NEJMoa2308719

Ultrasound Blood-Brain Barrier Opening and Aducanumab in Alzheimer's Disease

N Engl J Med. 2024 Jan 4;390(1):55-62. doi: 10.1056/NEJMoa2308719.

Authors

Ali R Rezai¹, Pierre-Francois D'Haese¹, Victor Finomore¹, Jeffrey Carpenter¹, Manish Ranjan¹, Kirk Wilhelmsen¹, Rashi I Mehta¹, Peng Wang¹, Umer Najib¹, Camila Vieira Ligo Teixeira¹, Tasneem Arsiwala¹, Abdul Tarabishy¹, Padmashree Tirumalai¹, Daniel O Claassen¹, Sally Hodder¹, Marc W Haut¹

Affiliation

¹ From the Departments of Neurosurgery (A.R.R., P.-F.D., M.R.), Neuroradiology (P.-F.D., J.C., R.I.M., P.W., A.T.), Neuroscience (A.R.R., V.F., C.V.L.T., T.A., P.T., M.W.H., R.I.M.), Neurology (K.W., U.N., M.W.H.), and Behavioral Medicine and Psychiatry (M.W.H.), Rockefeller Neuroscience Institute, Department of Medicine (S.H.), and West Virginia Clinical and Translational Science Institute (S.H.), West Virginia University, Morgantown; and the Department of Neurology, Vanderbilt University, Nashville (D.O.C.).

PMID: 38169490
DOI: 10.1056/NEJMoa2308719

Abstract

Antiamyloid antibodies have been used to reduce cerebral amyloid-beta (Aβ) load in patients with Alzheimer's disease. We applied focused ultrasound with each of six monthly aducanumab infusions to temporarily open the blood-brain barrier with the goal of enhancing amyloid removal in selected brain regions in three participants over a period of 6 months. The reduction in the level of Aβ was numerically greater in regions treated with focused ultrasound than in the homologous regions in the contralateral hemisphere that were not treated with focused ultrasound, as measured by fluorine-18 florbetaben positron-emission tomography. Cognitive tests and safety evaluations were conducted over a period of 30 to 180 days after treatment. (Funded by the Harry T. Mangurian, Jr. Foundation and the West Virginia University Rockefeller Neuroscience Institute.).

MeSH terms

Alzheimer Disease* / diagnosis
Alzheimer Disease* / diagnostic imaging
Alzheimer Disease* / drug therapy
Amyloid beta-Peptides / analysis
Antibodies, Monoclonal, Humanized / administration & dosage
Antibodies, Monoclonal, Humanized / therapeutic use
Blood-Brain Barrier* / metabolism
Brain / blood supply
Brain / diagnostic imaging
Humans
Positron-Emission Tomography / methods
Ultrasonic Therapy*

Substances

aducanumab
Amyloid beta-Peptides
Antibodies, Monoclonal, Humanized