R.Burge at bay.cc.kcl.ac.uk (Richard Burge) writes:
>How do prion diseases relate to Alzheimer's disease? The pathology looks
>incredibly similar, yet I'm assuming (ask me how much I _know_ about
>Alzheimer's!) that PrP is not involved, as I haven't seen it splashed all over
>the front cover of Nature or anything.
>Are the amyloid plaques the same as those found in prion diseases? If not,
>could they be formed by a similar mechanism - i.e. is there another prion
>protein, as yet undiscovered, underlying Alzheimer's disease?
Hello again, Richard!
The amyloid plaques aren't the same, in that Alz-plaques comprise chiefly BA4,
and prion disease plaquesvirtually uniquely PrP. As you know, 'amyloid' just
means anything which reacts with Congo Red, due to having a suitable bit of
beta-pleated-sheet in its structure, so there's this structural similarity
between the two diseases.
On top of that, the codon 198 point mutant form of GSS, so far found only in one
(very big) kindred in Indiana, USA, has neurofibrillary tangles! These are
morphologically and immunohistochemically identical to those pretty much common
to Alzheimer's. No one has yet drawn anything from this, but surely Occam's
Razor dictates that some common factor is causing NFT's in both instances, and
the similar-structured bit of the amyloid is the obvious candidate.
Add to this that PrP and BA4 are both small membrane-bound proteins in the first
place, one of which seems to be mis-folded and the other mis-cleaved, and some
sort of common process has to be seen as lying at the root of both.
Any more suggestions from the Alzheimer's side of the equation?
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Nev Percy ; spbcnsp at ucl.ac.uk