Basic Science and Pathogenesis

Area of Science:

• Neuroscience
• Pathology
• Traumatic Brain Injury Research

Background:

• Tau protein misfolding and aggregation into neurofibrillary tangles are hallmarks of tauopathies.
• Traumatic brain injury (TBI) is a risk factor for tauopathy onset and progression.
• Mechanisms of TBI-derived tau polymorph dissemination are not well understood.

Purpose of the Study:

• To investigate if TBI-derived tau polymorphs can initiate pathological tau formation.
• To determine if different TBI types lead to distinct tau pathogenic trajectories.
• To elucidate the role of neuroinflammation in TBI-induced tauopathy.

Main Methods:

• Wild-type mice were injected with TBI-derived tau polymorphs from sham, single-blast (SB), or repeated-blast (RB) conditions.
• Cognitive and motor functions were assessed using behavioral assays at 2 and 8 months post-injection.
• Tau aggregation, glial activation, inflammasome formation, and TBI biomarkers were analyzed.

Main Results:

• Repeated-blast TBI-derived tau polymorphs (RB-BDTPs) induced significant cognitive and motor deficits.
• RB-BDTPs promoted toxic tau aggregate formation in the hippocampus, which spread to cortical layers over time.
• RB-BDTP exposure increased glial activation, NLRP3 inflammasome formation, and S100B aggregation, indicating neuroinflammation.

Conclusions:

• TBI-BDTPs can initiate and propagate tau pathology, contributing to tauopathies.
• Neuroinflammation, including glial activation and inflammasome formation, is closely linked to TBI-induced tau pathology.
• This study enhances understanding of the interplay between TBI, tauopathy, and neuroinflammation.