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Neurocognitive testing (NCT) results following low dose hemi/ whole brain irradiation in genetically altered Alzheimer’s Dementia (AD) animal models

Alvaro A. Martinez

Statement of the Problem: The use of low dose radiation has been shown to be effective in the resolution of non CNS amyloidosis. Our consortium began looking at various hemi brain and whole brain low dose radiation doses to determine its impact on amyloid and neurocognitive function (NCT). Methodology & Theoretical Orientation: The Detroit group used the APPswePSEN1dE9 murine model, and tested NCT using the Morris Water Maze. The animals received whole brain radiation of 5 x 2 Gy at age 64 week and were tested 5 days before treatment and 8 weeks after treatment. Spatial learning and memory was assessed. The Geneva group used the TgF344-AD rat model. Female animals were treated with 5 x 2 Gy hemi brain irradiation at age 15 months and tested 3 weeks and 3 months after treatment. Open field (locomotor activity) and y maze (working memory) testing were assessed. Control animals were also tested. Animals were sacrificed after testing to determine amyloid-beta plaque changes. Findings: Both models showed a statistically significant improvement in cognitive abilities in the treated animals. Data from Detroit I shown in Fig.1 The treated group displayed significantly reduced latencies (31.0±17.6 seconds) compared to the untreated group (53.9±14.9 seconds) across trials on day 5 (p = 0.03). These differences were not due to baseline ambulatory /swimming velocities. The Geneva animals showed increased spatial memory index and decreased hyperactivity at 3 months.The test for younger males showed a clear decrease in TSPO in bilateral hippocampi. At sacrifice the Detroit group had noted reduction in amyloid plaque density. The Geneva group could not document a reduction in amyloid density but this may be due to a much higher plaque density in this model. Conclusion & Significance: Based on these results we continue to evaluate the use of different daily / total dose schedules and the use of targeted therapies to determine the role they may play in the treatment of AD.