Researchers have identified evidence that the brain’s waste-clearing system may become impaired during the earliest stages of synucleinopathy, a group of neurodegenerative disorders that includes Parkinson’s disease. The findings suggest that reduced cerebrospinal fluid (CSF) drainage could serve as an early biomarker for disease development.

The brain relies on cerebrospinal fluid to remove metabolic waste, including toxic proteins that accumulate over time. As people age, this drainage process becomes less efficient, allowing waste products to build up and potentially contribute to inflammation and neurodegeneration.

Scientists have identified two major pathways involved in CSF drainage. One passes through the cribriform plate near the olfactory bulb, where tiny fluid channels gradually close with age due to bone growth. The other, known as the glymphatic system, clears waste along blood vessels but becomes less effective as the movement of fluid through these vessels declines over time.

Reduced CSF drainage is believed to hinder the brain’s ability to remove harmful protein aggregates, including alpha-synuclein, the protein associated with Parkinson’s disease and related disorders. The resulting accumulation of waste may also trigger chronic inflammation in the brain, further accelerating disease progression.

In a new study, researchers used magnetic resonance imaging (MRI) to examine changes in CSF circulation in people with isolated rapid eye movement (REM) sleep behavior disorder (iRBD), a condition widely recognized as one of the earliest warning signs of Parkinson’s disease and other synucleinopathies. During REM sleep, individuals with iRBD act out their dreams because the normal muscle paralysis associated with sleep is impaired.

The study compared MRI scans from 18 individuals with iRBD, 20 healthy young adults, and 18 healthy older adults. Researchers measured the volumes of cerebrospinal fluid, perivascular spaces, fluid-filled channels that support the brain’s waste-clearance system, and venous drainage structures.

Results showed that participants with iRBD had larger CSF and perivascular space volumes than healthy controls, but without a corresponding increase in the size of the brain’s venous drainage structures. According to the researchers, this pattern suggests fluid stagnation caused by impaired CSF filtration rather than healthy circulation.

The findings indicate that dysfunction of the brain’s glymphatic waste-clearing system may occur before the appearance of the motor symptoms typically associated with Parkinson’s disease. If confirmed in larger studies, MRI-based measurements of CSF dynamics could help identify individuals at risk for synucleinopathies earlier, opening opportunities for earlier intervention and monitoring.

Researchers note that further studies are needed to determine whether restoring normal CSF drainage can slow or prevent the progression of neurodegenerative diseases.