Transmission of cerebral amyloid pathology by peripheral administration of misfolded Aβ aggregates

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.

Automated summary

This study demonstrates that administration of Aβ seeds through various peripheral routes can accelerate the accumulation of Aβ in the brains of AD mouse models. Oral administration of brain extracts had no impact on brain pathology. The peripheral administration of Aβ seeds led to the generation of a large proportion of aggregates in blood vessels, suggesting a role of vascular transport in AD-related pathological changes.