Catalytic Effect of Amyloid-β on Native Tau Aggregation at Physiologically Relevant Concentrations

Authors

Rakhi Chowdhury, University of Nebraska Medical CenterFollow
Apu Chandra Das, University of Nebraska Medical CenterFollow
Ruan van Deventer, University of Nebraska Medical CenterFollow
Luda S. Shlyakhtenko, University of Nebraska Medical CenterFollow
Yuri L. Lyubchenko, University of Nebraska Medical CenterFollow

Document Type

Article

Journal Title

International Journal of Molecular Sciences

Publication Date

2025

Volume

26

Abstract

Alzheimer's disease (AD) is characterized by the accumulation and aggregation of tau and amyloid-β (Aβ). The pathophysiology and progression of AD are facilitated by the neurotoxic effects of these aggregated proteins, resulting in neurodegeneration and memory loss. In this context, the interaction between tau and Aβ42 is considered, but the mechanism underlying their pathogenic interplay remains unclear. Here, we addressed this question by studying the aggregation of full-length, unmodified tau and Aβ42 at physiologically low concentrations using atomic force microscopy (AFM). AFM imaging and data analyses demonstrate an increase in tau aggregation in the presence of Aβ42, characterized by increased sizes and number of aggregates. Importantly, tau aggregation occurs without the need for phosphorylation or any other post-translational changes. The analysis of the data demonstrates that tau and Aβ42 form co-aggregates, with no visible accumulation of Aβ42 aggregates alone. Given that the catalysis of tau aggregation by Aβ42 is observed at physiological low nanomolar concentrations of Aβ42, the finding suggests that such aggregation catalysis of tau by Aβ42 can be a molecular mechanism underlying the pathological tau aggregation process associated with the onset and development of Alzheimer's disease.

MeSH Headings

tau Proteins, Amyloid beta-Peptides, Humans, Microscopy, Atomic Force, Alzheimer Disease, Protein Aggregates, Peptide Fragments, Protein Aggregation, Pathological, Phosphorylation

DOI Link

10.3390/ijms262412128

ISSN

1422-0067

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Chowdhury, Rakhi; Das, Apu Chandra; van Deventer, Ruan; Shlyakhtenko, Luda S.; and Lyubchenko, Yuri L., "Catalytic Effect of Amyloid-β on Native Tau Aggregation at Physiologically Relevant Concentrations" (2025). Journal Articles: Pharmaceutical Sciences. 51.
https://digitalcommons.unmc.edu/cop_pharmsci_articles/51