Traumatic Brain Injury Accelerates Alzheimer’s Disease Pathology in the TgF344-AD Rat Model

Abstract: Background: Epidemiological evidence shows that Traumatic Brain Injury (TBI) is a risk factor for Alzheimer’s disease (AD). TBI and AD have common overlapping pathologies. However, the underlying mechanisms are not clearly understood, and there are no effective treatments for TBI and AD. Aim of the study is to test the effect of TBI on the progression of AD pathology and associated neurological and cognitive dysfunction in the TgF344 AD rat model. Methods: Male and female TgF344-AD rats (3 months old) were randomized to receive parasagittal fluid percussion injury, sham injury, or naïve (N=10-16 rats/group). Neurobehavioral tests (beam walk, beam balance, neuroscore) were performed on post-injury days 1-3 and 3 months after injury. Water maze test was performed 3 months after Injury, then rats were sacrificed, and the brains were removed for immunohistological analyses of Aβ, p-Tau, and neuroinflammation. Results: TBI TgF344-AD rats performed significantly worse in the beam balance, beam walk, and neuroscore tests on days 1-3 post-injury when compared to the Tg sham and naïve groups (2- vii way ANOVA). Three months post-injury, Tg TBI rats performed significantly worse in beam balance, neuroscore test (2-way ANOVA), and the water maze test (RM one-way ANOVA) when compared to Tg sham and naïve groups. Aβ plaques and neuroinflammation were significantly higher in Tg TBI rats. Conclusion: These results show impairment of neurological and cognitive functions, increased accumulation of Aβ plaques, and neuroinflammation in TgF344-AD rats subjected to TBI, thus suggesting that brain injury could increase the severity of AD pathology and associated cognitive dysfunction.

Name thesis:degree_name

Neuroscience (Doctoral)

Grantor

The University of Texas Medical Branch at Galveston

Year dc:date.issued

2025

Author dc:creator

• Mahmoud El-Said, Lubna Nagy

Advisor dc:contributor.advisor

• Micci, Maria (mmicci@utmb.edu)

Language dc:language.iso

English

Handle dc:identifier.uri

https://hdl.handle.net/2152.3/12847

OAI identifier oai:identifier

oai:utmb-ir.tdl.org:2152.3/12847