Exogenous induction of cerebral ß-amyloidogenesis is governed by agent and host

M Meyer-Luehmann, J Coomaraswamy, T Bolmont… - Science, 2006 - science.org
M Meyer-Luehmann, J Coomaraswamy, T Bolmont, S Kaeser, C Schaefer, E Kilger…
Science, 2006science.org
Protein aggregation is an established pathogenic mechanism in Alzheimer's disease, but
little is known about the initiation of this process in vivo. Intracerebral injection of dilute,
amyloid-β (Aβ)–containing brain extracts from humans with Alzheimer's disease or β-
amyloid precursor protein (APP) transgenic mice induced cerebral β-amyloidosis and
associated pathology in APP transgenic mice in a time-and concentration-dependent
manner. The seeding activity of brain extracts was reduced or abolished by Aβ …
Protein aggregation is an established pathogenic mechanism in Alzheimer's disease, but little is known about the initiation of this process in vivo. Intracerebral injection of dilute, amyloid-β (Aβ)–containing brain extracts from humans with Alzheimer's disease or β-amyloid precursor protein (APP) transgenic mice induced cerebral β-amyloidosis and associated pathology in APP transgenic mice in a time- and concentration-dependent manner. The seeding activity of brain extracts was reduced or abolished by Aβ immunodepletion, protein denaturation, or by Aβ immunization of the host. The phenotype of the exogenously induced amyloidosis depended on both the host and the source of the agent, suggesting the existence of polymorphic Aβ strains with varying biological activities reminiscent of prion strains.
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