Research Paper Volume 15, Issue 3 pp 630—649
Immune-mediated platelet depletion augments Alzheimer’s disease neuropathological hallmarks in APP-PS1 mice
- 1 Institute of Molecular Regenerative Medicine, Paracelsus Medical University, Salzburg, Austria
- 2 Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University, Salzburg, Austria
- 3 Institute of Experimental Neuroregeneration, Paracelsus Medical University, Salzburg, Austria
- 4 Department of Transfusion Medicine, University Clinic, Paracelsus Medical University, Salzburg, Austria
- 5 Austrian Cluster for Tissue Regeneration, Vienna, Austria
Received: August 1, 2022 Accepted: January 23, 2023 Published: February 1, 2023
https://doi.org/10.18632/aging.204502How to Cite
Copyright: © 2023 de Sousa 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.
Abstract
In Alzheimer’s disease (AD), platelets become dysfunctional and might contribute to amyloid beta deposition. Here, we depleted platelets in one-year-old APP Swedish PS1 dE9 (APP-PS1) transgenic mice for five days, using intraperitoneal injections of an anti-CD42b antibody, and assessed changes in cerebral amyloidosis, plaque-associated neuritic dystrophy and gliosis. In APP-PS1 female mice, platelet depletion shifted amyloid plaque size distribution towards bigger plaques and increased neuritic dystrophy in the hippocampus. In platelet-depleted females, plaque-associated Iba1+ microglia had lower amounts of fibrillar amyloid beta cargo and GFAP+ astrocytic processes showed a higher overlap with thioflavin S+ amyloid plaques. In contrast to the popular hypothesis that platelets foster plaque pathology, our data suggest that platelets might limit plaque growth and attenuate plaque-related neuritic dystrophy at advanced stages of amyloid plaque pathology in APP-PS1 female mice. Whether the changes in amyloid plaque pathology are due to a direct effect on amyloid beta deposition or are a consequence of altered glial function needs to be further elucidated.
Abbreviations
Abeta: amyloid beta; AD: Alzheimer’s disease; APP: amyloid precursor protein; APP-PS1: APP Swedish PS1dE9 mice; CAA: cerebral amyloid angiopathy; IgG: immunoglobulins; GP: glycoprotein; MO: somatomotor cortex; PS1: presenilin 1; SS: somatosensory cortex; αCD42b: anti-CD42b antibody.