Intravenous injection of beta-amyloid seeds promotes cerebral amyloid angiopathy (CAA)

Seeding and spread of beta-amyloid (A beta) pathologies have been considered to be based on prion-like mechanisms. However, limited transmissibility of A beta seeding activity upon peripheral exposure would represent a key difference to prions, not only in terms of pathogenesis but also in terms of potential transmission of disease. We partially characterized the seeded A beta amyloidosis after intracerebral injection of various brain homogenates in APP/PS1 mice. One particularly seed-laden homogenate was selected to investigate the development of A beta pathologies after intravenous exposure. We report here that a single intravenous injection of an Alzheimer disease patient's-brain extract into APP/PS1 recipient mice led to cerebral amyloid angiopathy within 180 days post injection. Thus, vascular proteinopathies such as CAA are transmissible in mice via the intravenous route of peripheral exposure.