Is there a link between tau protein and amyloid plaques in alzeihmer's disease?

[hitmankratos]

Hi,

 

I was wondering if there is a link between the hyperphosphorylation of tau protein and amyloid plaques in alzeihmer's disease?

Are both present in Alzeihmer's?

[ennui]

This is a very thorny question. I used to research amyloid structure and I'm still not quite clear on the whole issue. There's still ongoing debate as to whether Alzheimer's Disease (AD) is caused by amyloid or tau.

 

Broadly speaking, there are two camps: people who think that amyloid is responsible for AD, and people who think that amyloid has been given undue attention and that tau deserves more investigation. One Nature article even went so far as to call the amyloid camp "Church of the Holy Amyloid", because they are very devoted to the theory. (There's an excellent article called "The Amyloid Code" in Nature Medicine which discusses the contention in layman's terms, written by Apoorva Mandavilli).

 

If you view the literature, you'll see AD classified differentially as either an amyloidosis or a tauopathy. The amyloid hypothesis is more popular, but the tau hypothesis is gaining a foothold.

 

I'm not sure if hyperphosphorylated tau is found in all AD autopsies, but it is quite commonly found intracellularly -- whereas amyloid is extracellular. New papers (particularly from C. Dobson, a big name in the field) seem to like the idea of calling AD a 'spectrum disease', with various causative agents. Perhaps in the future it will be separated into several similar diseases, just like diabetes.

 

In my opinion, AD isn't caused by the mature amyloid plaques or tau - but by the toxic oligomers that precede fibril formation. It could be that the amyloid and tau plaques are providing a protective role, a "least worst option" to deal with the toxic species. This is a newish theory which is becoming increasingly attractive.

 

Sorry if this is a long non-answer, but it's a very complicated issue. The article I mentioned above is a good primer for the debate.