Effects of Diminished Cerebrospinal Fluid Flow in the Spinal Canal on Amyloid Pathophysiology in Vervet Monkeys

Translational models using nonhuman primates provide valuable insights into the pathological changes associated with human brain aging. This study investigates the vervet monkey (Chlorocebus aethiops sabaeus) as a model for age-related Alzheimer's disease (AD)-like amyloid clearance impairment. The cerebrospinal fluid (CSF) plays a crucial role as a transport medium for waste clearance from the brain's interstitial space to lymphatic vessels.

To test the hypothesis that diminished CSF perfusion in the central nervous system contributes to AD pathophysiology, we quantified CSF flow dynamics (i.e. stroke volume, amplitude and peak flow) in the spinal canal via phase-contrast MRI and examined its association with age and AD fluid biomarkers in 16 female vervet monkeys aged from 10 to 27 years.

Strong negative correlations were observed between CSF flow metrics across the cardiac cycle and age (ρ = -0.68 to -0.83), and positive correlations were found between CSF flow metrics and CSF Aβ42/40 ratio (ρ = 0.67 to 0.84), while plasma biomarkers showed no correlation with CSF flow metrics. Age-adjusted analyses demonstrated moderate correlations between CSF flow and CSF Aβ42/40 ratio (ρ = 0.45 to 0.75).

These findings suggest that diminished CSF flow dynamics in the central nervous system could serve as a valuable imaging marker for impaired amyloid clearance, reflecting early-stage AD-like pathology.