Temporal Pattern of Neuroinflammation Associated with a Low Glycemic Index Diet in the 5xFAD Mouse Model of Alzheimer's Disease

Alzheimer's disease (AD) is associated with brain amyloid-beta (A beta) peptide accumulation and neuroinflammation. Currants, a low glycemic index dried fruit, and their components display pleiotropic neuroprotective effects in AD. We examined how diet containing 5% Corinthian currant paste (CurD) administered in 1-month-old 5xFAD mice for 1, 3, and 6 months affects A beta levels and neuroinflammation in comparison to control diet (ConD) or sugar-matched diet containing 3.5% glucose/fructose (GFD). No change in serum glucose or insulin levels was observed among the three groups. CurD administered for 3 months reduced brain A beta 42 levels in male mice as compared to ConD and GFD, but after 6 months, A beta 42 levels were increased in mice both on CurD and GFD compared to ConD. CurD for 3 months also reduced TNF alpha and IL-1 beta levels in male and female mouse cortex homogenates compared to ConD and GFD. However, after 6 months, TNF alpha levels were increased in cortex homogenates of mice both on CurD and GFD as compared to ConD. A similar pattern was observed for TNF alpha-expressing cells, mostly co-expressing the microglial marker CD11b, in mouse hippocampus. IL-1 beta levels were similarly increased in the brain of all groups after 6 months. Furthermore, a time dependent decrease of secreted TNF alpha levels was found in BV2 microglial cells treated with currant phenolic extract as compared to glucose/fructose solution. Overall, our findings suggest that a short-term currant consumption reduces neuroinflammation in SxFAD mice as compared to sugar-matched or control diet, but longer-term intake of currant or sugar-matched diet enhances neuroinflammation.