Radiation, either encountered in the environment or given clinically as a cancer treatment, can damage healthy tissue causing long-lasting loss of normal function. Animal research suggests that even low doses of particular types of high energy particle radiation can both cause these side effects in the brain and alter degenerative conditions like Alzheimer’s disease. We are developing research tools to better understand how radiation exposure impacts the brain so that we may ultimately improve cancer treatment and protect people who are exposed to unwanted radiation.
We use cultured human cells to model Alzheimer’s disease and then expose these cells to gamma radiation and high energy particle radiation at the NASA Space Radiation Laboratory at the Department of Energy’s Brookhaven National Laboratory. When comparing irradiated cells to unirradiated cells, we find little change after high energy particle radiation. However, after gamma radiation, we observe dose-dependent increases in specific protein levels associated with the progression of Alzheimer’s disease. This finding is of particular note because this effect occurs at doses lower than those commonly used for cancer treatment. We are further investigating these cell models for a more precise understanding of how radiation interacts with Alzheimer’s disease.
Background: Cranial radiotherapy patients suffer long-term cognitive deficits, and even relatively low doses of heavy ion radiation alter behavior and neurodegenerative disease progression in rodent models. The relationship between neurodegenerative disease and radiation-induced damage is understudied. We are developing in vitro neural models to investigate these connections for risk assessment and therapeutics screening.
Methods: Human neuron-astrocyte cocultures modeling Alzheimer’s disease were irradiated at Brigham and Women’s Hospital with 0-2 Gy of gamma radiation or at Brookhaven National Lab (BNL) with 0-2 Gy of gamma radiation or 0.5 Gy or 0.75 Gy of the simplified 5-ion galactic cosmic ray simulator (GCRsim).
Results: Gamma exposure, but not GCRsim, produced a consistent elevation of insoluble amyloid beta (Aβ) levels in all experiments and produced a dose-dependent increase in Aβ42/40 ratio in the later stage disease model. This finding is of particular note because 2 Gy is a typical dose for a single fraction of whole brain radiotherapy. Radiation altered sAPPα/β ratios independently of increasing insoluble Aβ species. Little to no effect was observed on levels of MAP tau, cell number, or neuronal or astrocyte marker expression. Altogether, we show evidence that radiation may alter the progression of Aβ pathology.
Funding: 80NSSC18K0810 (CAL)