Biomarkers.

Area of Science:

• Neurology
• Neuroimaging
• Pathology

Background:

• Periventricular white matter hyperintensities (pWMH) are common in Alzheimer's disease (AD), often attributed to ischemia or demyelination.
• Deep medullary veins (DMVs) venulopathy, specifically occlusive collagenosis, is increasingly implicated in pWMH development.
• Venous stasis and lymphatic system dysfunction may contribute to excessive extracellular fluid accumulation, leading to chronic edema.

Purpose of the Study:

• To investigate the in vivo association between confluent pWMH and DMVs in AD patients.
• To identify radiological and pathological evidence supporting DMV venulopathy as a cause of pWMH and associated edema.
• To correlate imaging findings with pathological data for validation.

Main Methods:

• Included 88 AD patients and 33 controls with confluent pWMH on T2/FLAIR MRI.
• Defined DMVs and measured their spatial relationship with pWMH.
• Assessed radiological signs of edema, including sparing of compact white matter tracts and dynamic pWMH changes over time.
• Quantified perivascular spaces and lacunes, with 13 imaging-pathological correlations for validation.

Main Results:

• Confluent pWMH significantly co-located with identified DMVs.
• A strong association was found between pWMH volume and the number of DMVs.
• Pathological analysis revealed venous collagenosis in large and small venules as significant predictors of pWMH.

Conclusions:

• Confluent pWMH in AD patients are strongly associated with visualizable DMVs, suggesting venous insufficiency due to collagenosis.
• In vivo evidence supports chronic edema, indicated by compact fiber tract sparing and reversible pWMH progression.
• Findings suggest DMV venous insufficiency is a primary cause of pWMH, leading to vasogenic edema and extracellular fluid accumulation.