Saturday, June 27, 2009

Alzheimers and BSE: Prions are not Tau

While sniffing around BSE research in the aftermath of the Tau protein paper find I came upon this quite interesting review. A quick pubmed of the author suggests that BSE is, in her book, a viral infection by a currently uncharacterised virus about 25nm across. I'm not experienced enough at looking at electron micrographs to tell how convincing her pictures are, but they certainly look OK to me.

If she is correct then Prof Ebringer is wrong on this one, as he feels that the TSEs are auto immune attacks comparable to MS.

The biggest problem with the virus hypothesis is the effect of converting the virus to ash and still having it retain its infectivity. I'm a bit puzzled as to how formalin fixation might enhance the virulence of a virus too. This is not typical behaviour of virus particles. Where as sticking ash or formalin fixed gunk in to a brain may do enough of the right sort of damage to trigger an auto immune attack.

On top of this there is the fact that SCID (severe combined immunodeficient) mice are extremely resistant to BSE. How many viral problems are blunted by having a crippled immune system?

The problem here for the auto immune hypothesis is that while SCID mice are very resistant to BSE, they are not completely so. This is less of a problem to me as even SCID mice have some residual functional immune tissue and auto immune attack does not seem to be wholly dependent on antibodies, it probably uses all sorts of cells.

But ultimately it is becoming clearer that the prion hypothesis is probably wrong because the better the purification of putative infectious prion proteins, the lower the infectivity. I would guess that synthetic prion proteins will prove to be fully harmless unless their injection in to a mouse's brain does as much damage as injecting ash.

Add to this the limited ability of the brain to produce disease specific pathologies (ie most end stage diseases look similar!). CJD looks VERY like MS to a histopathologist and simply injecting TNFalpha in to the eye produces lesions indistinguishable from CJD in the optic nerve!

I think the jury is definitely out on this one but it will be interesting to watch the progress of the prion hypothesis and whether prions turn out to be neurotoxic at all.

Peter

1 comment:

Ken said...

"as he feels that the TSEs are auto immune attacks comparable to MS."

'Auto-immune' diseases are cryptic; too common for the causation to be a result of natural - and purifying- selection.

And it's not just auto-immune diseases that's true of. INFECTIOUS CAUSATION OF DISEASE: AN EVOLUTIONARY PERSPECTIVE