First Aid-Kit Alzheimers disease hypothesis

 

The ”First-Aid-Kit AD-hypothesis” - where ”First aid kit” is assigned to the APP protein - is based on the observations that APP, expressed in neurons, has an important function to stimulate neurogenesis and remodelling in the healing process after a trauma, and acts neuroprotective. Furthermore, this regulatory protein is processed to give Abeta peptides, which have important multi-functional roles in the defense within the brain. These components are normally considered ”bad guys” and are regarded as the primary cause of the initialization of AD, according to the amyloid and cascade hypotheses.

 

Contrary to that view, according to the ”First-aid-kit AD-hypothesis” these Abeta peptides play an important defense role, acting as anti-microbiotic peptides killing invading bacterial and fungal microorganisms, acting as a metal chelator neutraliziing metal ions that are toxic to the brain, acting as sealer of micro-lesions of the BBB, being an inhibitor of clot formation within the vessels, but sealing on the outside wall, acting as trapper of resistant infectious agents such as parasites to encapsulate them, interacting with virus (HSV1 blocker) to inhibit viral multiplication, stimulating the immune system to increased activity by complement activation

Upstream event could be initiation of inflammation by toxic moleucles entering the brain through an aging, leaky BBB, or a BBB becoming leaking due to xx sensitivity, or after micro-bleedings. Alternatively damages caused by invading infectious agents like bacteria or virus and the subsequent inflammatory response with TNF as one conductor, stimulating the expression of APP and Abeta.

 

This hypothesis is not contradictory to other hypotheses, such as the vascular AD hypothesis or the amyloid hypothesis, but it does not support the medication with anti-Abeta substances as a primary choice to treat initial AD, but instead look for the underlying cause to the over-expression of Abeta whether it could be infections, vascular problems or inflammatory response to leaking BBB etc and make attempts to cure this underlying disease. Intervention to block Abeta should be a secondary measure to treat an over-active defense response in the brain, or when the clearance mechanism for Abeta is compromised.