Plaque fibrillization?

Question

I would like to (hypothetically) determine what causes diffuse amyloid plaques to fibrillize and become classic plaques -- those which are are associated with Alzheimer's disease. Could someone with knowledge on neuropathology please give me detailed suggestions as to what kind of procedures and technology to incorporate in order to examine some of the cellular components involved in this problem??
Thanks a lot!

Answer 1

Hmm. Well if we can answer that do you want to share the nobel prize?

The classical assay to investigate how proteins bind to each other is called co-immunoprecipitation. Essentially you allow proteins A and B to mix, then you extract protein B. If your extraction of protein B contains protein A, then the two bind to each other. Using this method you could see if a novel protein binds to beta-amyloid.

You could also to classical immunohistochemistry to probe the make up of diffuse and fibrile plaques.

Genetically modified Knock-out animals or other protein knock down techniques could tell you whether other proteins were involed in the conversion of diffuse to amyloid plaques.

Also, it is likely that the agregation of beta-amyloid relies on protein misfolding. One can now use NMR to study the shape of proteins which is far easier than older x-ray crystolography techneques.

Hope those ideas help.