Exogenous Aß seeds induce Aß depositions in the blood vessels rather than the brain parenchyma, independently of Aß strain-specific information.

ABSTRACT

Little is known about the effects of parenchymal or vascular amyloid ß peptide (Aß) deposition in the brain. We hypothesized that Aß strain-specific information defines whether Aß deposits on the brain parenchyma or blood vessels. We investigated 12 autopsied patients with different severities of Aß plaques and cerebral amyloid angiopathy (CAA), and performed a seeding study using an Alzheimer's disease (AD) mouse model in which brain homogenates derived from the autopsied patients were injected intracerebrally. Based on the predominant pathological features, we classified the autopsied patients into four groups AD, CAA, AD + CAA, and less Aß. One year after the injection, the pathological and biochemical features of Aß in the autopsied human brains were not preserved in the human brain extract-injected mice. The CAA counts in the mice injected with all four types of human brain extracts were significantly higher than those in mice injected with PBS. Interestingly, parenchymal and vascular Aß depositions were observed in the mice that were injected with the human brain homogenate from the less Aß group. The Aß and CAA seeding activities, which had significant positive correlations with the Aß oligomer ratio in the human brain extracts, were significantly higher in the human brain homogenate from the less Aß group than in the other three groups. These results indicate that exogenous Aß seeds from different Aß pathologies induced Aß deposition in the blood vessels rather than the brain parenchyma without being influenced by Aß strain-specific information, which might be why CAA is a predominant feature of Aß pathology in iatrogenic transmission cases. Furthermore, our results suggest that iatrogenic transmission of Aß pathology might occur due to contamination of brain tissues from patients with little Aß pathology, and the development of inactivation methods for Aß seeding activity to prevent iatrogenic transmission is urgently required.