Anti-inflammatory effects of 64Zn-aspartate is accompanied by cognitive improvements in rats with Aβ1-40-induced alzheimer disease.

Alzheimer disease (AD) is a debilitating progressive dementia, whose pathophysiology is not fully understood. Chronic inflammation is now widely accepted as one of the key features of AD pathogenesis. Because of this, anti-inflammatory preparations are considered as putative disease modifying agents. A new compound of zinc aspartate with enriched light atoms 64Zn (64Zn-asp) was evaluated as a possible anti-AD agent using Aβ1-40-induced AD model. Intrahippocampal Aβ1-40 injection resulted in pronounced neuroinflammation, as was evidenced by increased phagocytic activity, augmented reactive oxygen species generation, and up-regulated CD86 and CD206 expression by microglia. In rats with Aβ1-40-induced AD, persistent systemic inflammation was also registered, as was ascertained by significantly increased white blood cell-based inflammatory indices and development of anemia of inflammation. Neuro- and systemic inflammation in rats was accompanied by hippocampal dopamine neuron loss, as well as by impairment of short-term and remote spatial memory and cognitive flexibility. Intravenous 64Zn-asp administration rats with AD was associated with returning all microglia indicators to normal range. All aforementioned features of systemic inflammation were not observed in these animals. Anti-inflammatory 64Zn-asp effect was strongly correlated with improvement of short-term spatial memory and cognitive flexibility, and moderately-with betterment of remote spatial memory. These results demonstrated that i.v. 64Zn-asp administration could reverse the inflammatory and, as a result, cognitive effects of intra-hippocampal Aβ1-40 in rats. Therefore, its use may be a viable approach in the complex therapeutic strategy for AD.