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Katzmarski, Natalie; Ziegler-Waldkirch, Stephanie; Scheffler, Nina; Witt, Christian; Abou-Ajram, Claudia; Nuscher, Brigitte; Prinz, Marco; Haass, Christian; Meyer-Luehmann, Melanie (2020): A beta oligomers trigger and accelerate A beta seeding. In: Brain Pathology, Vol. 30, No. 1: pp. 36-45
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Aggregation of amyloid-beta (A beta) that leads to the formation of plaques in Alzheimer's disease (AD) occurs through the stepwise formation of oligomers and fibrils. An earlier onset of aggregation is obtained upon intracerebral injection of A beta-containing brain homogenate into human APP transgenic mice that follows a prion-like seeding mechanism. Immunoprecipitation of these brain extracts with anti-A beta oligomer antibodies or passive immunization of the recipient animals abrogated the observed seeding activity, although induced A beta deposition was still evident. Here, we establish that, together with A beta monomers, A beta oligomers trigger the initial phase of A beta seeding and that the depletion of oligomeric A beta delays the aggregation process, leading to a transient reduction of seed-induced A beta deposits. This work extends the current knowledge about the role of A beta oligomers beyond its cytotoxic nature by pointing to a role in the initiation of A beta aggregation in vivo. We conclude that A beta oligomers are important for the early initiation phase of the seeding process.