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<p>Alzheimer’s disease (AD) is marked by the abnormal aggregation of amyloid-beta peptides within the central nervous system. The formation of amyloid fibrils from amyloid-beta peptides is a hallmark of AD Here, we demonstrate that the aggregation of amyloid-beta 42 spreads both spatially and temporally. By measuring the spatial propagation of amyloid-beta in macroscopic capillaries and performing Monte Carlo simulations, we show that this spreading occurs through a diffusion mechanism involving oligomers in solution. These species, catalytically produced through&#xa0;spontaneous secondary nucleation, significantly accelerate the propagation velocity of the reaction wavefront. Our findings suggest that, in addition to their potential role in toxicity, these oligomers in solution are key drivers of the spatial spreading of aggregation and can therefore be considered key targets for therapeutic intervention.</p>

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Oligomers mediate the spatial transmission of Aβ peptide aggregation

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月20日

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  • Quentin Peter,
  • Chris Taylor,
  • Urszula Lapinska,
  • Jiapeng Wei,
  • Thomas C. T. Michaels,
  • Paolo Arosio,
  • Sara Linse,
  • Tuomas P. J. Knowles

摘要

Alzheimer’s disease (AD) is marked by the abnormal aggregation of amyloid-beta peptides within the central nervous system. The formation of amyloid fibrils from amyloid-beta peptides is a hallmark of AD Here, we demonstrate that the aggregation of amyloid-beta 42 spreads both spatially and temporally. By measuring the spatial propagation of amyloid-beta in macroscopic capillaries and performing Monte Carlo simulations, we show that this spreading occurs through a diffusion mechanism involving oligomers in solution. These species, catalytically produced through spontaneous secondary nucleation, significantly accelerate the propagation velocity of the reaction wavefront. Our findings suggest that, in addition to their potential role in toxicity, these oligomers in solution are key drivers of the spatial spreading of aggregation and can therefore be considered key targets for therapeutic intervention.