Curcuminoids enhance amyloid-beta uptake by macrophages of Alzheimer's disease patients.

J Alzheimers Dis. 2006;10(1):1-7

 

Due to poor understanding of mechanisms regulating amyloid-beta (Aβ) processing and brain clearance, advancement in therapy for Alzheimer’s disease (AD) has been complicated, at least in part.

Multiple factors have been attributed to Aβ accumulation in AD brain, such as interaction between Aβ–reactive T cells and microglia leading to differentiation of microglia into either phagocytes or antigen presenting cells with unclear neuroprotective role, ligation of CD40 on microglia by CD40L and inhibition of complement activation.

It has been known that physiologically in middle-aged and older normal people macrophages and microglia are involved in Aβ clearance but found to be defective in AD patients.

However, immunomodulatory therapies, such as those by Curcumin and insulin-like growth factor are found to be useful in enhancing brain clearance of Aβ in animal models.

 

Objective:

To evaluate immune modulation effects of Curcuminoids (Curcumin C3 Complex®) on effector cells of the human innate immune system and AD macrophages in vitro.

 

Study Design:

  • Eleven AD patients were chosen for testing but macrophage cultures could be established only from six
  • Normal age-matched control subjects were also involved in the study
  • Peripheral blood mononuclear cells (PBMCs) were separated from EDTA-anticoagulated blood
  • Around 100,000 PBMCs were isolated and cultured for 7–14 days at 37 ⁰C maintaining standard conditions and by following standard protocol
  • During incubation, it was observed that AD macrophages were poorly differentiated and more loosely adherent when compared to control macrophages
  • Differentiated macrophages were then treated with Curcumin C3 Complex® (0.1 μM) in the medium overnight

 

Results:

  • Immunofluorescence microscopy and confocal microscopy images demonstrated that complete internalization of Aβ by control macrophages, whereas AD macrophages bind Aβ only on the surface and showed defective phagocytosis
  • Hence, a significant uptake of Aβ was shown by control macrophages at baseline compared to AD macrophages
  • A significant increase (p<0.001) in the uptake of Aβ was seen when AD macrophages were treated with 0.1 μM Curcuminoids, whereas no improvement was observed in control macrophages

 

Conclusion:

Curcuminoids could be used for immune modulation of the innate immune system, which might be helpful for assessing the ability of patients to respond to immunomodulatory therapy.

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