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Evidence for aggregation-independent, PrP C -mediated Aβ cellular internalization
Abstract
Significance: Amyloid β (Aβ) aggregation has been the therapeutic target of several Alzheimer’s disease (AD) clinical trials. Aβ exists in many different aggregated forms, making it exceedingly challenging to target. Evidence links intracellular Aβ accumulation and AD pathogenesis. We report that amino acids 1 to 30 of Aβ, Aβ (1–30), do not aggregate yet display cellular uptake stereospecificity when compared to its mirror image, suggesting that Aβ uptake is predominantly receptor-mediated and may be independent from its aggregation state. Additionally, we found Aβ (1–30) internalization to depend on PrP C expression. Aβ (1–30) thus represents a powerful tool to study mechanisms of Aβ cellular internalization and suggests that Aβ uptake could be modulated by therapeutically targeting high-affinity Aβ receptors.
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“Given that PrPC can bind APP and can alter levels of Aβ40 and Aβ42 [38]”
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Cites
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Di Caro, V., Cho, E., Thiel, J., Lizama, B. N., Koel-Simmelink, M. J. A., Pandey, K., Duong, D., Seyfried, N. T., Grundman, M., Teunissen, C. E., et al. (2026) · Alzheimer's Research & Therapy · doi:10.1186/s13195-026-02025-4 · Cited by 1
Metadata
- Authors
- Foley, A. R., Roseman, G. P., Chan, K., Smart, A., Finn, T. S., Yang, K., Lokey, R. S., Millhauser, G. L., & Raskatov, J. A.
- Affiliations
- Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2020-11-02
- Volume
- 117
- Issue
- 46
- Pages
- 28625-28631
- ISSN
- 0027-8424
- 1091-6490
- Cited by
- 38
- References
- 15
- Language
- en
- Funders
- HHS | National Institutes of Health (2R25GM058903-20-IMSD, R21AG058074, R35GM131781, S10OD024980, S10OD018455, GM131135)
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