Leukoaraiosis (LA), an age-related white matter degeneration, is thought to be caused
by chronic ischemia. To understand the pathogenesis of LA, we studied the pathology,
particularly of the blood vessels, in 186 brains [84 of them with magnetic resonance
imaging (MRI)] over the past 10 years. With normal aging, there is gradual thickening
of the walls of periventricular veins and venules with collagen subtypes I and III.
This venous collagenosis (VC) was increased in brains with LA. Occasionally, LA lesions
are not periventricular, but nearer the cortex. In such cases, the most severe VC
occurs in the LA lesion rather than near the ventricle. Therefore, LA and VC are not
independent degenerative processes coincidentally found near the ventricles, and although
damage to the ependyma could be a cause of VC, it cannot be the only cause. Whether
VC precedes LA is unknown, but our experience suggests that severe VC is usually accompanied
by LA. Arteriolar tortuosity, another age-related vascular pathology, is common in
LA. Our thick celloidin sections show three-dimensional views of tortuous arterioles.
The tortuosity is much more severe in the white matter and there is considerable loss
of parenchyma around them. Staining for collagen IV in the basal lamina reveals tortuous
vessels in an "empty bag" that represents the limits of the surrounding parenchyma.
These enlarged perivascular spaces correspond to état criblé. The demyelination in
LA lesions is accompanied by loss of cells, mostly oligodendrocytes. In studies of
apoptosis in LA, we found increased apoptosis within the lesion compared to the surrounding
white matter. In conclusion, our studies support the concept that LA results from
chronic ischemia due to age-related vascular pathology.