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Aβ oligomers trigger and accelerate Aβ seeding
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DOI：10.1111/bpa.12734.png)
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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.
Keyword:
Alzheimer's disease
A beta seeding
A beta oligomers
amyloid-beta plaques
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Titration of biologically active amyloid-β seeds in a transgenic mouse model of Alzheimer's disease.png)
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OAAI分享收藏Seed-induced Aβ deposition is modulated by microglia under environmental enrichment in a mouse model of Alzheimer's disease在阿尔茨海默氏病小鼠模型中，种子诱导的a β 沉积在环境富集下受到小胶质细胞的调节EMBO JOURNALOAAI
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