Ischemic blood-brain barrier and amyloid in white matter as etiological factors in leukoaraiosis

Background Pathology of white matter, which is observed in ischemic brain, indicates that similar processes contribute to Alzheimer's disease development. These injuries have been seen in the subcortical and periventricular regions. Periventricular white matter changes in ischemic and Alzheimer's disease brain, referred to as leukoaraiosis, are responsible for changes in memory, cognition and behavior. It is not clear whether the blood-brain barrier in ischemic periventricular white matter is altered in aged animals

Methods We studied blood-brain barrier changes with amyloid precursor protein staining around blood-brain barrier vessels. Rats were made ischemic by cardiac arrest. Blood-brain barrier insufficiency, accumulation of amyloid precursor protein and platelets around blood-brain barrier vessels were investigated in ischemic periventricular white matter up to 1-year survival.

Findings Ischemic periventricualr white matter demonstrated enduring blood-brain barrier changes. Toxic fragments of amyloid precursor protein deposits were associated with the blood-brain barrier vessels. Moreover our investigation revealed platelet aggregates in- and outside blood-brain barrier vessels. Toxic parts of amyloid precursor protein and platelet aggregates correlated very well with bloodbrain barrier permeability.

Conclusions Progressive injury of the ischemic periventricular white matter may be caused not only by a degeneration of neurons destroyed during ischemia but also by damage in blood-brain barrier. Chronic ischemic blood-brain barrier insufficiency with accumulation of toxic components of amyloid precursor protein in the periventricular white matter perivascular space, may gradually over a lifetime, progress to leukoaraiosis and finally to severe dementia