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Oligomers mediate the spatial transmission of Aβ peptide aggregation

Peter, Quentin ; Taylor, Chris ; Lapinska, Urszula ; Wei, Jiapeng ; Michaels, Thomas C.T. ; Arosio, Paolo ; Linse, Sara LU and Knowles, Tuomas P.J. (2026) In Communications Chemistry 9(1).
Abstract

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... (More)

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.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Communications Chemistry
volume
9
issue
1
article number
35
publisher
Springer Nature
external identifiers
  • scopus:105028253042
  • pmid:41559153
ISSN
2399-3669
DOI
10.1038/s42004-025-01837-z
language
English
LU publication?
yes
id
9bdfb956-5dee-483d-95f7-5748cb40839b
date added to LUP
2026-02-17 15:04:10
date last changed
2026-02-18 03:00:05
@article{9bdfb956-5dee-483d-95f7-5748cb40839b,
  abstract     = {{<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 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>}},
  author       = {{Peter, Quentin and Taylor, Chris and Lapinska, Urszula and Wei, Jiapeng and Michaels, Thomas C.T. and Arosio, Paolo and Linse, Sara and Knowles, Tuomas P.J.}},
  issn         = {{2399-3669}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Springer Nature}},
  series       = {{Communications Chemistry}},
  title        = {{Oligomers mediate the spatial transmission of Aβ peptide aggregation}},
  url          = {{http://dx.doi.org/10.1038/s42004-025-01837-z}},
  doi          = {{10.1038/s42004-025-01837-z}},
  volume       = {{9}},
  year         = {{2026}},
}