Research Paper Volume 13, Issue 17 pp 20935—20961

Hyperbaric oxygen therapy alleviates vascular dysfunction and amyloid burden in an Alzheimer’s disease mouse model and in elderly patients

Ronit Shapira1, , Amos Gdalyahu1, , Irit Gottfried1, , Efrat Sasson4, , Amir Hadanny4, , Shai Efrati2,3,4, , Pablo Blinder1,2, , Uri Ashery1,2, ,

  • 1 School of Neurobiology, Biochemistry and Biophysics, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel-Aviv, Israel
  • 2 Sagol School of Neuroscience, Tel Aviv University, Tel-Aviv, Israel
  • 3 Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel
  • 4 Sagol Center for Hyperbaric Medicine and Research, Assaf Harofeh Medical Center, Be’er Ya’akov, Israel

Received: March 4, 2021       Accepted: August 10, 2021       Published: September 9, 2021
How to Cite

Copyright: © 2021 Shapira et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Vascular dysfunction is entwined with aging and in the pathogenesis of Alzheimer’s disease (AD) and contributes to reduced cerebral blood flow (CBF) and consequently, hypoxia. Hyperbaric oxygen therapy (HBOT) is in clinical use for a wide range of medical conditions. In the current study, we exposed 5XFAD mice, a well-studied AD model that presents impaired cognitive abilities, to HBOT and then investigated the therapeutical effects using two-photon live animal imaging, behavioral tasks, and biochemical and histological analysis. HBOT increased arteriolar luminal diameter and elevated CBF, thus contributing to reduced hypoxia. Furthermore, HBOT reduced amyloid burden by reducing the volume of pre-existing plaques and attenuating the formation of new ones. This was associated with changes in amyloid precursor protein processing, elevated degradation and clearance of Aß protein and improved behavior of 5XFAD mice. Hence, our findings are consistent with the effects of HBOT being mediated partially through a persistent structural change in blood vessels that reduces brain hypoxia. Motivated by these findings, we exposed elderly patients with significant memory loss at baseline to HBOT and observed an increase in CBF and improvement in cognitive performances. This study demonstrates HBOT efficacy in hypoxia-related neurological conditions, particularly in AD and aging.


AD: Alzheimer’s disease; α- CTF: α-secretase-cleaved C-terminal fragment; Aβ: amyloid beta; APP: amyloid precursor protein; ATA: atmosphere absolute; BACE1: β-secretase-1; β-CTF: β-secretase-1 cleaved C-terminal fragment; CAA: cerebral amyloid angiopathy; CBF: cerebral blood flow; HBOT: hyperbaric oxygen therapy; HIF-1: hypoxia inducible factor-1; IDE: insulin-degrading enzyme; LRP1: low-density lipoprotein receptor-related protein 1; MCI: mild cognitive impairment; PSE: presenilin 1; RBCs: red blood cells; TBI: traumatic brain injury.