Alzheimers and Tumor Necrosis Factor Alpha

Sorry I will not provide links.

Tumor Necrosis Factor Alpha (TNF alpha) is an inflamatory peptide hormone. A soluble protein which is based on part of the receptor for TNF alpha is used to treat arthritis. It has been noted from health insurance records that this treatment is associated with a much reduced risk of Alzheimer’s disease.

One important aspect of Alzheimer’s is the formation of placques (clumps) of a peptide called amyloid beta. Amyloid beta oligimers (like about 50 of them stuck to each other) induce cells in the brain called microglia to release, among other things, TNF alpha. TNF alpha causes neurons to synthesize amyloid beta precursor and 2 proteases which process the precursor to amyloid beta.

This suggests that inhibiting TNF alpha in the brain might prevent Alzheimer’s or slow its progression.

A problem is getting a peptide across the blood brain barrier. This problem has been solved taking advantage of the transferrin receptor which causes transferring to cross the blood brain barrier (bringing Iron to the brain). If a peptide is modified adding a (not to tight binding) antibody to the transferrin receptor, then it crosses the blood brain barrier.

Solubilized TNF alpha receptor is used to treat arthritis. It is a pain (literally if mildly) as peptides can’t be taken orally as they are digested. They can be injected. Maybe used in nose drops. It would be nice if one subcutaneous injection gradually released peptide with a half life of one month. This technology exists (ask Daniel Santi).

I have not read the articles I googled. I don’t know what stage this research has reached, but I think it is time for Phase III trials.

It seems the assertions with no links was not well received. Here are cites

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