Preclinical Evidence

Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo
J Biol Chem. 2005;280(7):5892-901
The progression of Alzheimer’s disease (AD) is believed to be the result of progressive accumulation of amyloid-beta (Aβ) aggregates and a cascade of events, such as neurotoxicity, oxidative damage, and inflammation thereafter.

Several therapeutic interventions have been adapted to target Aβ production, including inhibiting secretase, increasing Aβ clearance with amyloid vaccines or blocking Aβ aggregation (with antibodies, peptides or small organic molecules that selectively bind and inhibit Aβ aggregate and fibril formation).

Curcumin, a potent anti-inflammatory and antioxidant agent, has been known to inhibit oxidative damage, inflammation, cognitive deficits and amyloid accumulation. However, it is not clear whether Curcumin has the ability to reduce plaques in vivo by effects on aggregation.

To investigate whether efficacy of Curcumin in AD models could be explained by effects on Aβ aggregation.

Study Design:
  • APPsw Tg2576 transgenic mice were placed on 500 ppm Curcumin or control safflower oil-based test diets and aged until 22 months
  • The mice were anesthetized and injected with 200 µl of Curcumin/PBS (50 µM) or only PBS as control into the right carotid artery over a 5-min period
  • After 1 h, mice were perfused and brains were removed and snap-frozen
  • Later brain tissues cryosections were air-dried for 10 min in the dark and coverslipped for fluorescence protection
  • Immunolabeling was examined in various cortical and hippocampal areas of animals, and image analysis was conducted for plaque pathology
  • Amyloid levels were evaluated in the cortex of both control and curcumin-fed animals
Results and Discussion:
  • No plaque staining was seen in PBS-treated control animals, whereas Curcumin-injection demonstrated brightly labelled plaques, suggesting that Curcumin can cross the blood-brain barrier and bind to plaques in transgenic mice after oral feeding or peripheral injection
  • A significant decrease in amyloid levels was witnessed in aged Tg2576 mice, which were on Curcumin diet, beginning at 17 months after established amyloid deposition

Curcumin at low dose decreased amyloid formation in aged animals, thus providing a rationale for clinical trials for Curcumin in the prevention or even treatment of AD.