Abstract

Several of the main amyloid degrading enzymes are members of the M13 peptidase family (neprilysin) (NEP) NEP2 and the end of the line converting enzymes (ECE-1 and-2.A distinct metallopeptidase insulin-degrading enzyme (IDE), also contributes to AB degradation in the brain).  Somatostatin is a substrate.  (The substance on which an enzyme acts). of insulin-degrading enzyme (IDE) as well as a modulator of its activity and expression. 

Somatostatin increases neprilysin which attacks and degrades amyloid beta. The higher somatostatin levels the more neprilysin is activated.  Again there are marginal levels of somatostatin in the Alzheimer’s brain and cerebrospinal fluid.  Insulin degrading enzyme can reduce obviously insulin but also acts on Amyloid beta too.  However, somatostatin is its substrate which totally undermines this enzyme from being of any significant level.  Endothelin converting enzyme-1 does not effectively reduce amyloid beta to a healthy status in Alzheimer’s disease.

As there is nothing to lower amyloid beta levels there is a gradual accumulation, which creates severe problems.  Tau plaques are produced as a roll on effect of this series of events, as amyloid beta competes with insulin to engage with the same receptors; the over abundant amyloid beta leaves the insulin nowhere to go or nowhere to engage.  This is then a type of insulin resistance which is linked to Alzheimer’s disease. Consequently the high insulin levels degrade healthy Tau.

https://www.frontiersin.org/articles/10.3389/fncel.2019.00017/full

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4166351/

Textbook of Medical Physiology 7^th Edition 1986, Arthur C Guyton