Galactic Cosmic Radiation Leads to Cognitive Impairment and Increased Aβ Plaque Accumulation in a Mouse Model of Alzheimer's Disease

Galactic Cosmic Radiation consisting of high-energy, high-charged (HZE) particles poses a significant threat to future astronauts in deep space. Aside from cancer, concerns have been raised about late degenerative risks, including effects on the brain. In this study we examined the effects of Fe-56 particle irradiation in an APP/PS1 mouse model of Alzheimer's disease (AD). We demonstrated 6 months after exposure to 10 and 100 cGy Fe-56 radiation at 1 GeV/mu, that APP/PS1 mice show decreased cognitive abilities measured by contextual fear conditioning and novel object recognition tests. Furthermore, in male mice we saw acceleration of A beta plaque pathology using Congo red and 6E10 staining, which was further confirmed by ELISA measures of A beta isoforms. Increases were not due to higher levels of amyloid precursor protein (APP) or increased cleavage as measured by levels of the beta C-terminal fragment of APP. Additionally, we saw no change in microglial activation levels judging by CD68 and Iba-1 immunoreactivities in and around A beta plaques or insulin degrading enzyme, which has been shown to degrade A beta. However, immunohistochemical analysis of ICAM-1 showed evidence of endothelial activation after 100 cGy irradiation in male mice, suggesting possible alterations in A beta trafficking through the blood brain barrier as a possible cause of plaque increase. Overall, our results show for the first time that HZE particle radiation can increase A beta plaque pathology in an APP/PS1 mouse model of AD.