The Role of Cerebrospinal Fluid Flow in the Subarachnoid Space in Beta‐Amyloid Clearance

Abstract

AbstractBackgroundRecent studies identified the lymphatic drainage system in the brain. Here, cerebrospinal fluid (CSF) carries waste from brain tissue. However, it is still not well understood how CSF flow in the brain affects waste removal. In this study, we hypothesize that CSF flow patterns in the subarachnoid space will be correlated with beta‐amyloid deposition in the brain.MethodThirteen participants (7 Cognitively Normal and 2 Mild Cognitive Impairment, Age = 68±7.7 yrs. M/F = 5/4) who had prior amyloid PET imaging were recruited for CSF flow MRI from the Wake Forest Alzheimer’s Disease Research Center. The CSF flow patterns during the cardiac cycle were measured using the phase‐contrast MRI at the cerebral aqueduct, pontine cistern and cerebellomedullary cistern (Fig. 1). Images were acquired for 40 cardiac cycles with a pulse oximeter and CSF flow profiles were estimated using the retrospective cardiac gating method. PET Amyloid burden in the whole gray matter (GM) was measured as the standardized update value ratio (SUVR, cerebellar gray matter as a reference region) from the prior PET imaging and corresponding MRI.ResultCSF flow amplitude normalized by the brain tissue volume demonstrated moderate to strong correlations with beta‐Amyloid SUVR in GM (Fig. 2); Pearson’s correlation coefficient (rho) was ‐0.59 (p = 0.036) and ‐0.84 (p = 0.004) at pontine cistern and cerebellomedullary cistern, respectively. The lateral ventricle volume normalized by brain volume was also moderately correlated with GM SUVR (rho = 0.495).ConclusionAt an early stage of AD, the CSF circulation in the subarachnoid space could be correlated with beta‐Amyloid deposition. Therefore, CSF flow in the subarachnoid space could be a useful imaging marker to predict the clearance of beta‐amyloid in the brain.