Alzheimer's Imaging Consortium.

Area of Science:

• Neuropathology
• Neuroimaging
• Vascular Biology

Background:

• White matter hyperintensities (WMHs) are visible on MRI but their underlying pathology is unclear.
• WMHs can result from neurodegenerative, vascular, or neuroinflammatory processes.
• Understanding WMH pathology is crucial for diagnosing and treating neurological conditions.

Purpose of the Study:

• To investigate the neuropathological substrates of WMHs.
• To compare pathology in WMHs versus normal-appearing white matter (NAWM).
• To identify specific cellular and vascular changes associated with WMHs.

Main Methods:

• Analyzed 52 MRI-matched tissue blocks comparing WMH and NAWM regions.
• Assessed small vessel pathology (hyalinization, arteriolosclerosis), axon loss, demyelination, neurofilament degradation, and gliosis.
• Utilized standardized staining and semi-automated quantification (HALO) with paired analyses.

Main Results:

• Perivascular space (PVS) size, collagenosis, and gliosis were significantly greater in WMHs compared to NAWM.
• Astrocytic injury was significant only in paired analyses, suggesting localized pathology.
• No significant differences were found in myelination or neurofilament light chain markers between WMH and NAWM.

Conclusions:

• Vascular and glial pathology are prevalent in WMHs.
• Astrocytic changes may indicate localized pathology within WMHs.
• The absence of significant neuronal pathology markers could be due to less severe injury or overshadowing by diffuse aging-related white matter changes.