Effect Of Serum-Solubilized Curcumin On Plaques In Alzheimer's Disease Transgenic Mice

Progress Updates

In an initial round of experiments carried out by Dr. Quitschke’s team of researchers, curcumin was solubilized in blood serum derived from and tested on rats of the same strain without adverse effect. Particular concerns were that curcumin might have toxic effects or that the injected serum might induce allergic reactions. However, using the same protocol on mice engineered to have Alzheimer’s disease did produce adverse reactions after multiple injections. This necessitated the use of an alternative delivery vehicle for getting curcumin into solution (i.e. cyclodextrin).

For the analysis of plaque prevention, the Alzheimer’s mice were intravenously injected with the new curcumin cyclodextrin solutions once per week for 6 months. For the remaining 6-8 weeks, injections needed to be continued subcutaneously due to extensive deterioration of the tail vein at the site of injections. Preliminary analysis showed a 10-15% reduction of plaque load in treated animals relative to controls. The ability of intravenously injected curcumin solutions to resolve existing plaques was assessed by injecting Alzheimer’s mice twice per week between the ages of 11-12 months. For this set of experiments, the team used a curcumin dose 4-fold higher than in the plaque prevention experiments. This resulted in a plaque reduction of about 30% relative to controls. Although these results are encouraging, they did not provide an extensive reduction of plaques. Therefore, the team further investigated the bioavailability of injected curcumin.

They found that intravenously injected curcumin was rapidly cleared from circulation and tissues by metabolic conversion. After 60 minutes, essentially all of the curcumin and metabolites were eliminated from the system. Surprisingly, the curcumin levels achieved in the brain were unexpectedly high and maximum concentrations were delayed until several minutes after injection. In contrast to serum and other organs, the brain didn’t contain certain inactive curcumin metabolites (called conjugated metabolites). Instead, relatively high levels of curcumin remained for up to 30 minutes while being locally metabolized (converted by reduction). This raises the possibility that curcumin levels in the brain could be high enough to enable binding to amyloid plaques, and that plaque prevention and resolution could be further enhanced by increasing the exposure to curcumin.