Microglia activation and Lipid droplet pathology in animal models of type 2 diabetes and Alzheimer’s disease

Alzheimer’s disease (AD) is the most common cause of dementia. Globally, AD is among the 7 leading cause of death and significant affect the quality of life for the individuals affected and their relatives (World Health Organization, 2020). People with type 2 diabetes mellitus (T2DM) has an increased risk of developing AD, perhaps because the pathological processes in the brain are partly overlapping. Both AD and T2DM display increasing prevalence in the population. Research on pathological mechanisms for AD and diabetes-related dementia is important to acquire treatment options and improve life quality. Research over the past decade has shown increasing evidence for an important role of neuroinflammation in AD pathology. Furthermore, recent studies have shown an interest in neutral lipids stored in lipid droplets in the brain as a possible mechanism for neuroinflammation (Marschallinger et al., 2020). Also, lipid droplets have been shown to accumulate in microglia, which are the resident immune cells of the brain and are identified as having a key role in neuroinflammation. The purpose of the present study is to investigate the potential effects of microglia activation and the accumulation of lipid droplets in the brain of mice with T2DM and AD. Animal models for AD and T2DM were used to investigate microglia activation and lipid droplets pathology in the mouse brain. Exercised obese diabetic mice were also used in Morris water maze, a behavioral test to assess spatial memory and learning. Further, immunohistochemistry was performed to study microglia activation and lipid droplet accumulation. We found that microglia activation was higher in affected brain regions in mice with T2DM and AD: The AD mice had significantly higher microglia activation than its wild type control mice and the obese diabetic mice tended towards a higher state of microglia activation compared to their control genotype. Interestingly, no significant difference in lipid droplets accumulation was found between any of the animal models or genotypes. The T2DM mice tended towards performing worse than their non-diabetic littermates in the Morris water maze test for spatial memory. Furthermore, we found exercise to have a positive effect on cognitive function and mice with T2DM having an impaired memory performance, but a larger group of animals is needed for a final conclusion to be drawn. Overall, these results suggest that neuroinflammation plays a key role in neurodegenerative diseases, although lipid droplets do not appear to affect the microglia activation