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Treating a Mouse Model of Alzheimers Disease with Exposures to Arrays of Parallel, Thin Planes of X-Rays

JR Nassimi*, DC Heaney, KN Hirsch, CR Messina, T Zimmerman, JE Davis, ME Schweitzer, L Bangiyev, FA Dilmanian, Stony Brook University Hospital, Stony Brook, NY


(Sunday, 7/14/2019)  

Room: ePoster Forums

Purpose: Alzheimer’s disease (AD) is the most common form of dementia among the elderly, affecting over five million individuals in the U.S. The pathological hallmarks of AD include accumulation in the brain of amyloid-Β(AΒ) plaques and tau neurofibrillary tangles. Whole-brain irradiation of a mouse model of AD with conventional—i.e., broad beam—x-rays has been shown to ablate AΒ plaques and improve cognitive performance in these mice. Furthermore, arrays of parallel, thin (~0.3 mm) planes of x-rays, called microbeams, spare CNS tissues at very high doses. Moreover, microbeams spare the glial system, allowing the necessary microglia to effectively clear AB debris.

Methods: Therefore, we propose that x-ray microbeams can be used to treat AD by ablating AB plaques while sparing the brain and using the spacing between beams to clear the remaining AB debris. In this study, the entire brains of AD-transgenic mice, excluding the brain stem, will be irradiated with either microbeams or conventional broad beams to comparatively evaluate the methods’ abilities to ablate AB plaques and improve cognitive function in this mouse model of AD. The mice will then be kept for three months post-irradiation. The mice will be subjected to a) cognitive tests, b) PET/MRI imaging to examine the reduction of AB plaques and the rate of plaque ablation/shrinkage, and c) histological evaluation after three months. The results will provide the optimal irradiation parameters as well as the minimum microbeam dose that produces effective plaque ablation and will ideally confirm that the necessary irradiations do not cause cognitive deficits.

Results: The goal is to develop a safe and effective AD treatment method that can be implemented anywhere.

Conclusion: For clinical use, the spacing between microbeams can be increased to prevent beam smearing caused by cardiac-induced brain pulsation.


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