Differences in amyloid-β and tau/p-tau deposition in blood-injected mouse brains using micro-syringe to mimic traumatic brain microhemorrhages

Abstract

Background: Cerebral microbleeds (CMBs) due to traumatic brain injuries (TBI) have been shown to lead to cognitive decline and impairment. CMBs caused by TBI may be associated with pathophysiological mechanisms involving inflammation and the accumulation of amyloid-β (Aβ), tau, and phosphorylated tau (p-tau), contributing to cognitive abnormalities. However, their relationships remain unclear.

Objectives: To test our hypothesis that Aβ, tau, and p-tau are accumulated and regulated separately in mice with injuries imitating CMBs from TBI, we studied.

Methods: Seven-week-old C57BL/6 male mice were injected with 15 μL of heparinized autologous blood or saline by micro-syringe into the front lobe. Expression profiles and regulation of Aβ, tau, and p-tau were assessed immunohistochemically over time.

Results: On day 7 after blood injection, Iba-1⁺ and S100B⁺ cells in damaged cortex adjacent to the injection site were higher than saline injection group and non-injected sham. On days 3-14, Aβ deposition were gradually increased but normalized by day 28. In contrast, tau/p-tau deposition gradually increased during days 14-28 and dispersed along the corticomedullary junction adjacent to hem deposits, indicating different expression profiles from Aβ. Deposits of Aβ, but not tau/p-tau, were phagocytosed by CD163⁺ macrophages increased by Gc-protein macrophage-activating factor during days 7-28, suggesting different mechanisms of deposition and regulation between Aβ and tau/p-tau.

Conclusion: Deposition and regulation differ between Aβ and tau/p-tau in mice with injuries mimicking CMBs from TBI. Further clarification of relationships between the pathologies of cognitive impairment and their neurodegenerative consequences is needed.

Keywords: Amyloid-β; Cognitive impairment; Tauopathy; Traumatic cerebral microbleed.