Research Paper Volume 13, Issue 5 pp 7644—7659
Platelets transport β-amyloid from the peripheral blood into the brain by destroying the blood-brain barrier to accelerate the process of Alzheimer's disease in mouse models
- 1 Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, P.R. China
- 2 Department of Science and Education, Guangdong Second Provincial General Hospital, Guangzhou, P.R. China
Received: November 13, 2020 Accepted: January 25, 2021 Published: March 5, 2021https://doi.org/10.18632/aging.202662
How to Cite
Copyright: © 2021 Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Extracellular aggregation of the β-amyloid (Aβ) peptide into toxic multimers in the brain is a prominent event occurring in the pathogenesis of Alzheimer’s disease (AD), and a large amount of Aβ in the blood is derived from platelets. Thus, we speculated that platelets may play an important role in the process of AD. We first investigated the changes in platelet Aβ secretion with age. Then, we injected platelets from aged amyloid precursor protein APP/PS1 mice into young C57 mice and assessed their memory capacity along with their brain and peripheral blood Aβ expression levels. The Aβ content in mouse platelets increased with age. Exogenously aged APP/PS1 platelets changed the permeability of the blood-brain barrier in vitro, accelerating Aβ deposition in the brain and increasing the Aβ content in peripheral blood, leading to learning and memory deficits in the recipient mice. Subsequently, aspirin was administered to mice as an inhibitor of platelet activation, which effectively alleviated these toxic processes. Finally, we chose an in vitro blood-brain barrier model to explore the possible cytotoxicity of these platelets.
Aβ: β-amyloid; AD: Alzheimer disease; SAMP8: senescence-accelerated mice prone 8; SAMR1: senescence-accelerated mice resistant 1; APP: amyloid precursor protein; BBB: blood-brain barrier; PRP: platelet-rich plasma; MWM: Morris water maze; OCT: optimal cutting temperature compound; ELISA: enzyme-linked immunosorbent assay; PBS: phosphate-buffered saline; TEER: trans-endothelial electrical resistance; CCK-8: Cell Counting Kit-8; IF: immunofluorescence; COX: cyclooxygenase.