Abstract
Seeding and spread of beta-amyloid (Aβ) pathologies have been considered to be based on prion-like mechanisms. However, limited transmissibility of Aβ 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 Aβ amyloidosis after intracerebral injection of various brain homogenates in APP/PS1 mice. One particularly seed-laden homogenate was selected to investigate the development of Aβ 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.
Highlights
Intracerebral injections of beta-amyloid (Aβ) require femtogram quantities of brain-derived Aβ seeds to induce an Alzheimer’s disease (AD)-like pathology in amyloid precursor protein (APP)-transgenic APP23 or tg2576 mice [7, 14, 18, 19]
The apparent ease of intracerebral transmission suggests that the seeding and spread of Aβ pathologies in brain tissue may - at least in part - occur in a manner similar to PrPSc-based prions [2, 13]
To demonstrate the development of an Aβ amyloidosis triggered by intracerebral exposure to Aβ seeds in our system, we injected various brain homogenates intracerebrally into 6–8 weeks old APP/PS1 mice
Summary
Intracerebral injections of beta-amyloid (Aβ) require femtogram quantities of brain-derived Aβ seeds to induce an Alzheimer’s disease (AD)-like pathology in amyloid precursor protein (APP)-transgenic APP23 or tg2576 mice [7, 14, 18, 19]. Introduction Intracerebral injections of beta-amyloid (Aβ) require femtogram quantities of brain-derived Aβ seeds to induce an Alzheimer’s disease (AD)-like pathology in amyloid precursor protein (APP)-transgenic APP23 or tg2576 mice [7, 14, 18, 19]. Oral, intraocular, intranasal, and intravenous administration of Aβ seeds did not promote development of AD-like pathologies in APP23 transgenic mice.
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