Abstract

Previous reports showed that brain A beta amyloidosis can be induced in animal models by exogenous administration of pre-formed aggregates. To date, only intra-peritoneal and intra-venous administrations are described as effective means to peripherally accelerate brain A beta amyloidosis by seeding. Here, we show that cerebral accumulation of A beta can be accelerated after exposing mouse models of Alzheimer's disease (AD) to A beta seeds by different peripheral routes of administration, including intra-peritoneal and intra-muscular. Interestingly, animals receiving drops of brain homogenate laden with A beta seeds in the eyes were efficiently induced. On the contrary, oral administration of large quantities of brain extracts from aged transgenic mice and AD patients did not have any effect in brain pathology. Importantly, pathological induction by peripheral administration of A beta seeds generated a large proportion of aggregates in blood vessels, suggesting vascular transport. This information highlights the role of peripheral tissues and body fluids in AD-related pathological changes.