Alzheimer’s disease is a chronic neurodegenerative disease that usually starts slowly and the process and development of the disease is associated with plaques and tangles in the brain. These plaques and tangles are referred to as amyloids which are aggregates of proteins that become folded into a shape that allows many copies of that protein to stick together.
The amyloid hypothesis (proposed in 1991 1) postulates that extracellular amyloid beta deposits are the fundamental cause of Alzheimer’s. As a result, Amyloid beta (Aβ or Abeta) proteins are the main component of the amyloid plaques found in the brains of Alzheimer patients. These peptides result from the amyloid precursor protein (APP) being converted by enzymes and yielding amyloid beta.
Excessive accumulation of amyloid beta can cause neurotoxic effects in the brain. Proactive efforts to minimize amyloid beta toxicity in the brain is necessary as an overall healthy neurological strategy. Such a strategy would encompass the following:
- Decrease amyloid beta protein production
- Decrease the aggregation or deposition of existing amyloid beta protein
- Improve the clearance of existing amyloid beta protein from the brain
- Prevent amyloid fibril formation of amyloid beta protein
One important mechanism that clears amyloid beta from the brain is Low density lipoprotein receptor-related protein 1 (LRP1). LPRI is a protein forming a receptor found in the plasma membrane of cells and is the major cell surface receptor for clearance of amyloid beta from brain interstitial fluid across the blood-brain barrier. 2
A study published in 2012 in the Proceedings of the National Academy of Sciences of the United States of America demonstrated the remarkable therapeutic effect of Ashwagandha (Withania somnifera) which up-regulated of liver LRPI and improved the mechanism for amyloid beta clearance from the brain.
The researchers found that using Withania somnifera extracts, comprising 75% withanolides and 20% withanosides, reversed plaque pathology and reduced the amyloid beta burden in middle-aged and old APP/PS1 mice through up-regulation of liver LRPI, leading to increased clearance of amyloid beta. 3 The dose of the withanolides and withanosides used is this study was high.
Withania somnifera is a plant in the Solanaceae (nightshade) family and is commonly knowns as:
- Indian ginseng
- Poison gooseberry
- Winter cherry
Withania somnifera consists of the following chemical constituents:
- steroidal lactones
- withaferin A