Traumatic brain injury and Alzheimer's disease related neurodegenerative diseases: Insights from animal models.

Alzheimer's disease and related neurodegenerative diseases (ADRD) represent a major global public health challenge, with their disease mechanisms remain largely unknown, and few treatments are available. Increasing epidemiological evidence underscores the critical role of traumatic brain injury (TBI) in the initiation and progression of ADRD, suggesting shared pathogenic mechanisms between these conditions. While there are still lack of perfect AD models in the field, TBI models may serve as useful and alternative platforms for investigating ADRD. In this review we delineate the definition and epidemiological characteristics of TBI. We further briefly compare the major experimental TBI animal models, outlining their respective strengths and limitations in replicating human neuropathology. Finally, we provide our perspective on potential mechanistic links between TBI and ND, including axonal injury, calcium homeostasis dysregulation, mitochondrial dysfunction, chronic neuroinflammation, blood-brain barrier disruption, and genetic susceptibility. We believe advancing preclinical and translational research on TBI not only enhances our understanding of the pathogenesis in ADRD but also holds promise for developing interventions to mitigate long-term consequences and improving clinical outcomes for many neurodegenerative diseases.