Beta Amyloid - Intervention Strategies

Intervention Strategies

Researchers in Alzheimer's disease have identified five strategies as possible interventions against amyloid:

• β-Secretase inhibitors. These work to block the first cleavage of APP outside of the cell.
• γ-Secretase inhibitors (e. g. semagacestat). These work to block the second cleavage of APP in the cell membrane and would then stop the subsequent formation of Aβ and its toxic fragments.
• Selective Aβ₄₂ lowering agents (e. g. tarenflurbil). These modulate γ-secretase to reduce Aβ₄₂ production in favor of other (shorter) Aβ versions.
• Immunotherapy. This stimulates the host immune system to recognize and attack Aβ, or provide antibodies that either prevent plaque deposition or enhance clearance of plaques or Aβ oligomers. One such beta-amyloid vaccine that is currently in clinical trials is CAD106.
• Anti-aggregation agents such as apomorphine. These prevent Aβ fragments from aggregating or clear aggregates once they are formed.

There is some indication that supplementation of the hormone melatonin may be effective against amyloid. Melatonin interacts with amyloid beta and inhibits its aggregation This anti-aggregatory activity occurs only through an interaction with dimers of the soluble amyloid beta peptide. Melatonin does not reverse fibril formation or oligomers of amyloid beta once they are formed. This is supported by experiments in transgenic mice which suggest that melatonin has the potential to prevent amyloid deposition if administered early in life, but it may not be efficacious to revert amyloid deposition or treat Alzheimer's disease.

This connection with melatonin, which regulates sleep, is strengthened by the recent research showing that the wakefulness inducing hormone orexin influences amyloid beta (see below). Interestingly, animal experiments show that melatonin may also correct mild elevations of cholesterol which is also an early risk factor for amyloid formation.

The cannabinoid HU-210 has been shown to prevent amyloid beta-promoted inflammation. The endocannabinoids anandamide and noladin ether have also been shown to be neuroprotective against amyloid beta in vitro.