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Heterotypic Amyloid β interactions facilitate amyloid assembly and modify amyloid structure

Konstantoulea, Katerina, Guerreiro, Patricia, Ramakers, Meine, Louros, Nikolaos, Aubrey, Liam D., Houben, Bert, Michiels, Emiel, De Vleeschouwer, Matthias, Lampi, Yulia, Ribeiro, Luís F, and others. (2022) Heterotypic Amyloid β interactions facilitate amyloid assembly and modify amyloid structure. The EMBO journal, 41 (2). ISSN 1460-2075. (doi:10.15252/embj.2021108591) (KAR id:93219)


It is still unclear why pathological amyloid deposition initiates in specific brain regions or why some cells or tissues are more susceptible than others. Amyloid deposition is determined by the self-assembly of short protein segments called aggregation-prone regions (APRs) that favour cross-β structure. Here, we investigated whether Aβ amyloid assembly can be modified by heterotypic interactions between Aβ APRs and short homologous segments in otherwise unrelated human proteins. Mining existing proteomics data of Aβ plaques from AD patients revealed an enrichment in proteins that harbour such homologous sequences to the Aβ APRs, suggesting heterotypic amyloid interactions may occur in patients. We identified homologous APRs from such proteins and show that they can modify Aβ assembly kinetics, fibril morphology and deposition pattern in vitro. Moreover, we found three of these proteins upon transient expression in an Aβ reporter cell line promote Aβ amyloid aggregation. Strikingly, we did not find a bias towards heterotypic interactions in plaques from AD mouse models where Aβ self-aggregation is observed. Based on these data, we propose that heterotypic APR interactions may play a hitherto unrealized role in amyloid-deposition diseases.

Item Type: Article
DOI/Identification number: 10.15252/embj.2021108591
Uncontrolled keywords: Alzheimer’s disease; amyloid beta ; heterotypic aggregation; toxicity
Subjects: Q Science
Q Science > QP Physiology (Living systems) > QP517 Biochemistry
Divisions: Divisions > Division of Natural Sciences > Biosciences
Funders: European Research Council (
Biotechnology and Biological Sciences Research Council (
Depositing User: Wei-Feng Xue
Date Deposited: 16 Feb 2022 15:26 UTC
Last Modified: 04 Mar 2024 17:50 UTC
Resource URI: (The current URI for this page, for reference purposes)

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