Your question: can we do something with our method in the case of prion diseases, would have implications also on Alzheimer, and we are at the moment interested in an early diagnosis. Now I said before that the disease cannot be triggered by single units, that came out of our paper. You need a co-operative, like in an allosteric enzyme, you need several subunits, or even a formation of little crystallites, so that you have a supersaturated solution and the infectious unit triggers that process of transformation. Well in both cases, what has been shown for the BSE is that you get plaque formation, very similar as in Alzheimer's disease. In other words there are decomposites of the protein in form of plaques which you can see under the microscope, and the co-operativity might well be connected with it. Be it as it may, it would yield us a very nice way of diagnosis, of early diagnosis, and that again is based on fluorescence correlation spectroscopy. But now we don't use the auto-correlation, we rather use cross-correlation and I must explain what I mean by that.
If you have a aggregate being the cause of the disease, then it means that several molecules have to get together, and when you can show that the infectious one does such a thing, then by proving the existence of these complexes you can very early diagnose the disease. And what we now do is we take two fluorescence dyes, and put one on part of the molecules and the other one on another part of the molecules, the non-infectious ones. Now in a case of non-infection these molecules remain separate and we see either the blue or the red fluorescence or the green fluorescence, but we see them separately. And what we do now is cross-correlation, that means we... you remember when I explained auto-correlation is that we measure products of intensities, an intensity at a given time, T, times the intensity at a moment afterwards, a T plus the other T. Now here we also measure products of intensity but not on time-scale. We now take intensity at a time T of the green fluorescence times the intensity at time T of the red. Now if they are separate, the molecules, these are independent quantities, and the product would be zero, apart from noise. But if they form a complex they fluoresce at the same time and then the product would be finite, and this method is very, very sensitive. And this is always in a disease an important point to see it as early as possible and then start with some anti-viral strategy or anti-disease strategy.
