Introduction: Mapping of microscopic changes in the perivascular space (PVS) of the cerebral cortex, beyond magnetic resonance-visible PVS in white matter, may enhance our ability to diagnose Alzheimer's disease (AD) early.

Methods: We used the cerebrospinal fluid (CSF) water fraction (CSFF), a magnetic resonance imaging-based biomarker, to characterize brain parenchymal CSF water, reflecting microscopic PVS in parenchyma. We measured CSFF and amyloid beta (Aβ) using 11 C Pittsburgh compound B positron emission tomography to investigate their relationship at both the subject and voxel levels.

Results: Our research has demonstrated a positive correlation between the parenchymal CSFF, a non-invasive imaging biomarker indicative of parenchymal glymphatic clearance, and Aβ deposition, observed at both individual and voxel-based assessments in the posterior cingulate cortex.

Discussion: This study shows that an increased parenchymal CSFF is associated with Aβ deposition, suggesting that CSFF could serve as a biomarker for brain glymphatic clearance, which can be used to detect early fluid changes in PVS predisposing individuals to the development of AD.

Highlights: Cerebrospinal fluid fraction (CSFF) could be a biomarker of parenchymal perivascular space. CSFF is positively associated with amyloid beta (Aβ) deposition at subject level. CSFF in an Aβ+ region is higher than in an Aβ- region in the posterior cingulate cortex. Correspondence is found between Aβ deposition and glymphatic clearance deficits measured by CSFF.