Genetic factors complicating recovery in patients with brain injury: Possible link between injury severity and posttraumatic neurodegeneration related to intracerebral amyloid deposition - A narrative review.

Background: Traumatic brain injury (TBI) may initiate long-term neurodegenerative processes that complicate postinjury recovery. Both severe and repetitive mild TBI are associated with dysregulated amyloid precursor protein processing and intracranial deposition of amyloid-beta (Aβ), a hallmark of neurodegenerative disease. The objective of the study is to summarize current evidence linking TBI with posttraumatic neurodegeneration, cerebral amyloid angiopathy (CAA), and genetically mediated susceptibility factors influencing recovery. Methods: A narrative review of relevant literature was performed with a focus on mechanisms of posttraumatic vascular amyloid deposition and the role of genetic predisposition. Results: TBI triggers secondary injury mechanisms, including persistent neuroinflammation, excitotoxicity, mitochondrial dysfunction, and blood-brain barrier disruption, which promote sustained intracerebral Aβ deposition and impaired clearance, which is closely associated with CAA and increased risk of lobar intracerebral hemorrhage. Iatrogenic CAA represents a distinct Aβ-related entity with prolonged incubation and heterogeneous clinical presentation. It seems that genetic susceptibility, particularly apolipoprotein E epsilon 4 (APOEε4), is associated with increased amyloid burden, more severe cerebral contusions, and poorer long-term functional outcomes following TBI. Conclusion: TBI may accelerate neurodegenerative and amyloid-related vascular processes that adversely affect recovery. Genetic predisposition, especially APOEε4, appears to modulate posttraumatic intracranial amyloid deposition and long-term outcomes, highlighting the importance of individualized risk assessment in patients with TBI.