Cerebral vascular amyloid deposition in rabbits with induced thyroglobulin immunity

Cerebral amyloid angiopathy (CAA) occurs in humans along with the neuritic amyloid plaques in Alzheimer's disease, in several familial (inherited) syndromes, and in a sporadic form that increases in prevalence with age to attain a rate of about 60% after age 90. In the non-Alzheimer conditions, it is often accompanied by cerebral hemorrhage and sometimes also by dementia. We report here the experimental induction of cerebrovascular amyloid (CVA) in thyroglobulin (Tg)-immunized rabbits. The vascular deposits in these rabbits are comparable to that seen in humans in that they primarily involve arterioles, venules, and capillaries and exhibit microscopic and ultrastructural characteristics similar to the human lesion. Prominent congophilic vascular lesions in the brain were seen in three out of six Tg-immunized rabbits, whereas less striking basement membrane thickening was evident in three other experimental animals, probably reflecting individual variations in vascular responses to actively induced Tg immunity. Occasional primitive amyloid plaques were also encountered adjacent to vascular lesions. These observations are of particular interest since in other experimental models, cerebral vascular amyloid deposits have not been observed, thus suggesting that immunopathogenic events induced by active Tg immunization may be unique in their effects on the cerebral vasculature.