Clinical Anatomy MSc Candidate University of Western Ontario London, Ontario, Canada
Abstract Body : Introduction: Adult-onset Leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a rare, fatal neurodegenerative disease that causes adult-onset dementia. One hallmark of ALSP are white matter hyperintensities (WMH) which can be detected on magnetic resonance imaging (MRI). Visible WMH reflect a variety of types of damage to the white matter of the brain and are associated with cognitive impairment and increased risk of dementia. Due to the white matter’s anatomical vulnerability to the effects of ischemia, alterations to the microvasculature are one established driver of white matter damage. On the other hand, the subcortical u-fibers, which possess a unique and rich blood supply, are preserved in ALSP. Despite this background, the vascular component underlying the white matter changes in ALSP has not been investigated. Thus, the perivascular space (PVS), which enlarge in other neurodegenerative diseases, presents a novel avenue for exploring the vascular underpinning of white matter degeneration in ALSP.
Objective: The objective of this study was to histologically characterize the PVS and vascular stenosis of ALSP patients by measuring and comparing the PVS in WMH and normal-appearing white matter regions of ASLP to healthy, control post-mortem brains.
Methods: Postmortem brains from 5 ALSP patients (n=5) and 5 control patients (n=5) were coronally sectioned at 8 µm and imaged using MRI to determine regions of WMH. Tissues were then stained using hematotoxin and eosin and the areas of the PVS were measured in the normal-appearing white matter, WMH regions, and subcortical u-fibers. These measurements were used to calculate the %PVS: the area of the PVS outside of the vessel relative to the vessel and surrounding PVS area combined. Unpaired t-tests were used to determine significant difference (p ≤ 0.05) between measurements in different brain regions and between ALSP and control tissue.
Results: In this study, it was determined that PVS area and %PVS area were significantly greater in WMH regions compared to normal-appearing white matter regions within ALSP patients. Additionally, in ALSP brain tissue PVS and %PVS were significantly smaller within the sub-cortical u-fibers compared to adjacent regions of WMH. Finally, in comparison to control tissue, WMH regions of ALSP tissue were found to have significantly larger PVS areas.
Significance: In this study, histology was used for the first time to investigate the PVS in white matter in ALSP. By characterizing this marker of ALSP at the white matter-vascular interface, the cascade of white matter degeneration observed in ALSP can be better understood. To expand on these potential vascular changes in ALSP patients, blood vessel stenosis will be evaluated to investigate a potential source of PVS enlargement in ALSP.
