The influence of intermittent hypercapnia on cerebrospinal fluid flow and clearance in Parkinson’s disease and healthy older adults

A failure of the glymphatic pathway to clear brain byproducts implicated in neurodegeneration may contribute to the pathophysiology of Parkinson's disease. The glymphatic pathway relies on vasomotion (rhythmic constriction and dilation of blood vessels) to drive cerebrospinal fluid through the interstitial space and clear waste from the brain. The current study demonstrated that intermittent hypercapnia, exposure to low levels of CO₂ in ON-OFF cycles, elicited vasomotion-induced cerebrospinal fluid inflow in both healthy controls and individuals with Parkinson's disease. The magnitude of the vasomotion-induced cerebrospinal fluid inflow in patients with Parkinson's disease was reduced relative to healthy controls. However, intermittent hypercapnia, administered in three 10-minute sessions totaling approximately 30 minutes, increased the appearance of total α-synuclein, neurofilament light, glial fibrillary acidic protein, amyloid β_1-42, amyloid β_1-40, and phosphorylated tau 217 in the plasma of both healthy controls and individuals with Parkinson's disease. This suggests that intermittent hypercapnia can be used to clear potentially toxic brain byproducts from the brain, highlighting its potential use as a disease modifying treatment.