Mechanisms of Hyperbaric Oxygen Chamber in the Prevention and Alleviation of Alzheimer’s Disease

I. Correcting Cerebral Hypoxia and Improving Cerebral Perfusion (Fundamental Mechanism)

• Increasing partial pressure of oxygen and diffusion: Inhalation of pure oxygen under hyperbaric conditions can increase arterial partial pressure of oxygen (PaO₂) by 10–20 times and significantly elevate blood oxygen content. The diffusion distance and speed of oxygen in brain tissue are greatly enhanced, effectively penetrating the blood-brain barrier and reversing hypoxia in key regions such as the hippocampus and cortex.
• Improving cerebrovascular function:
  • Selectively constricts over-dilated blood vessels and dilates under-perfused vessels, regulating cerebral blood flow distribution.
  • Increases cerebral microvascular density and promotes the formation of collateral circulation, improving long-term cerebral perfusion and reducing hypoxia-inducible factor (HIF-1α) levels.
• Relieving cerebral edema and lowering intracranial pressure: By constricting cerebral blood vessels and reducing exudation, HBOT alleviates hypoxia-induced cerebral edema and protects neurons.

II. Inhibiting Core Pathologies: Aβ Plaques and Tau Tangles

1. Reducing Aβ Deposition and Promoting Clearance

• Inhibiting Aβ production: Regulating the cleavage pathway of amyloid precursor protein (APP), reducing β-secretase activity, and decreasing Aβ generation.
• Promoting Aβ degradation and clearance:
  • Upregulating Aβ transporters such as low-density lipoprotein receptor-related protein 1 (LRP1) to enhance Aβ efflux across the blood-brain barrier.
  • Activating microglia to transform into a “surveillant/clearance phenotype” (increased branching, enhanced phagocytic ability), accelerating plaque phagocytosis and degradation.
  • Animal studies have shown that HBOT can reduce the volume of existing plaques and inhibit the formation of new plaques.

2. Inhibiting Tau Hyperphosphorylation

• Reducing the total level and activity of glycogen synthase kinase 3β (GSK3β), decreasing abnormal tau phosphorylation, thereby reducing the formation of neurofibrillary tangles (NFTs) and protecting microtubule structure and axonal transport.

III. Reducing Neuroinflammation and Regulating Microglial Function

• Inhibiting pro-inflammatory phenotypes: Reducing the release of pro-inflammatory factors such as IL-1β, TNF-α, and IL-6 from microglia, decreasing the “secondary damage” to neurons caused by neuroinflammation.
• Promoting anti-inflammatory/repair phenotypes: Inducing microglia to transform into a ramified morphology, increasing the secretion of anti-inflammatory factors such as IL-4 and IL-10, exerting neuroprotective and tissue-repairing effects.

IV. Repairing Mitochondrial Function and Counteracting Oxidative Stress

• Enhancing mitochondrial biogenesis and autophagy: Upregulating the PINK1/Parkin pathway, promoting mitophagy, removing damaged mitochondria, and maintaining mitochondrial quality control.
• Improving energy metabolism: Increasing ATP synthesis to improve neuronal energy supply and reverse the “energy crisis”.
• Anti-oxidative stress: Increasing the activity of endogenous antioxidant enzymes such as SOD and glutathione, scavenging ROS, reducing lipid peroxidation and DNA damage, and inhibiting neuronal apoptosis.

V. Promoting Neuroregeneration and Synaptic Repair

• Neurogenesis: Activating the proliferation and differentiation of neural stem cells in the hippocampus to replenish lost neurons.
• Synaptic plasticity: Upregulating neurotrophic factors such as BDNF, NT3, and NT4/5, promoting synaptogenesis via the MeCP2/p-CREB pathway, restoring synaptic density and function, and improving learning and memory.
• Inhibiting neuronal apoptosis: Upregulating anti-apoptotic proteins (e.g., Bcl-2) and downregulating pro-apoptotic proteins (e.g., Bax) to reduce neuronal loss.

VI. Overall Synergistic Effects and Clinical Significance

• Improved hypoxia → reduced Aβ/tau pathology → alleviated inflammation → mitochondrial repair → promoted neuroregeneration → improved cognition.
• Animal experiments (5xFAD, 3xTg models) confirmed that HBOT can significantly improve spatial memory and learning ability, reduce plaques and tangles, and protect neurons.
• Preliminary clinical studies have shown that in elderly patients with mild-to-moderate AD or memory impairment, HBOT can increase cerebral blood flow and improve cognitive scores with good safety.

Summary