Consequence of Ab immunization on the vasculature of human Alzheimer’s disease brain

A major feature of Alzheimer’s disease is the accumulation of amyloid-b peptide (Ab) in the brain both in the form of plaques in the cerebral cortex and in blood vessel as cerebral amyloid angiopathy (CAA). Experimental models and human clinical trials have shown that accumulation of Ab plaques can be reversed by immunotherapy. In this study, we hypothesized that Ab in plaques is solubilized by antibodies generated by immunization and drains via the perivascular pathway, detectable as an increase in cerebrovascular Ab. We have performed a follow up study of Alzheimer’s disease patients immunized against Ab42. Neuropatho-logical examination was performed on nine patients who died between four months and five years after their first immunization. Immunostaining for Ab40 and Ab42 was quantified and comparedwith that in unimmunized Alzheimer’s disease controls (n=11).Overall, compared with these controls, the group of immunized patients had approximately 14 times as many blood vessels containing Ab42 in the cerebral cortex (P_0.001) and seven times more in the leptomeninges (P=0.013); among the affected blood vessels in the immunized cases, most of them had full thickness and full circumference involvement of the vessel wall in the cortex (P=0.001), and in the leptomeninges (P=0.015).There was also a significantly higher level of cerebrovascular Ab40 in the immunized cases than in the unimmunized cases (cortex:P=0.009 and leptomeninges: P=0.002). In addition, the immunized patients showed a higher density of cortical microhaemorrhages and microvascular lesions than the unimmu