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Aging-US: Alleviating vascular dysfunction & amyloid burden in Alzheimer’s

10-25-2021

Aging-US published "Hyperbaric oxygen therapy alleviates vascular dysfunction and amyloid burden in an Alzheimer’s disease mouse model and in elderly patients" which reported that In the current study, the authors exposed 5XFAD mice, a well-studied AD model that presents impaired cognitive abilities, to HBOT and then investigated the therapeutic 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. Motivated by these findings, the authors 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.

Dr. Uri Ashery from The Tel Aviv University said, "In recent years, it has become clear that vascular dysfunction is entwined in the pathogenesis of Alzheimer’s disease (AD) and cognitive decline during aging."

Figure 8. CBF and cognitive function are improved following HBOT of patients CBF and cognitive functions of six patients suffering from memory decline at baseline and following 60 HBOT sessions. (A) Average normalized CBF maps (DSC) at baseline and post-HBOT. (B) Significant average CBF changes in Brodmann areas at baseline and post-HBOT. (C) Average cognitive domain scores (Neurotrax) at baseline and post-HBOT.

Vascular risk factors, such as obesity, diabetes, atherosclerosis, smoking and hypertension, are major risk factors for AD. Cerebral amyloid angiopathy, the deposition of Aβ peptide in cerebral vessel walls, is the most common vascular pathology in AD.

Both AD and CAA are associated with reduced cerebral blood flow, which precedes the clinical onset of dementia and correlates with the degree of cognitive impairment in AD. Hyperbaric oxygen therapy, the medical administration of 100% oxygen at environmental pressure greater than one atmosphere absolute, is in clinical use for a wide range of medical conditions.

At present, there are only 13 FDA-approved indications for HBOT, including non-healing ischemic wounds, post radiation injuries, decompression sickness, burn repair, carbon monoxide intoxication, and diabetic ulcers. At the same time, animal models offer major advantages in advancing our understanding of the cellular and molecular mechanisms leading to increased CBF.

Recently, it was shown that HBOT improved cognitive performance in animal models of Alzheimer’s disease, and improved the metabolic status and cognitive scores of AD and amnestic mild cognitive impairment patients.

HBOT improved cognitive performance in animal models of Alzheimer’s disease, and improved the metabolic status and cognitive scores of AD

The Ashery Research Team concluded in their Aging-US Research Output, "we showed here that HBOT offers multi-faceted neuroprotective effects on the complex pathology of Alzheimer’s disease and also improves CBF and cognition in humans. Targeting various pathways involved in the basic pathophysiology of AD may offer a more potent strategy for modifying disease progression. To this point, HBOT has been demonstrated to ameliorate the pathology and improve behavior in three AD mouse models, namely 3xTg-AD, 5XFAD and APP/PS1 mice [17, 36]. Given that HBOT is considered a safe and tolerable treatment currently being used in the clinic, the increasing number of clinical trials showing that HBOT improves cognitive function in patients suffering from chronic brain damage, the pre-clinical studies elucidating mechanisms of HBOT action, and the fact that there is presently no effective intervention for AD, HBOT should be considered as a therapeutic approach to slow the progression or even improve the pathophysiology responsible for this disease."

Full Text - https://www.aging-us.com/article/203485/text

Correspondence to: Uri Ashery email: uria@tauex.tau.ac.il

Keywords: Alzheimer's disease, hyperbaric oxygen therapy, vascular dysfunction, cerebral blood flow, amyloid burden

About Aging-US:

The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population.

The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.)

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