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One example to start with is the nucleus tuberalis lateralis (1A) . It is situated in the posterior part of the hypothalmus. It is interesting for many reasons. In the first place you can only find it in higher primates and in the human brain. It is evoultionarily a very recent nucleus. Secondly there is a tremendous accumulation of Alzheimer pre-tangle stage Alzheimer pathology as stained in this case by Alz-50. It is even such that you don't even need a microscope to see the pathology. One can just hold the section to the light and say "well this an Alzheimer patient". It has a tremendous staining even more dense than in many cortical areas. This is a double staining, it is for Alz-50 and amyloid, but you can hardly see any amyloid. This is an interesting point. This isn't a special case because there are some amyloid stained plaques here but yet there are many patients where you do not see any amyloid, but yet there is a tremendous accumulation of the pre-tangle stages. This means that in this area the whole process is starting without amyloid. There are many other examples of differences between the different components of Alzheimer's disease.

This is a higher magnification of the same area (1B). You can see the dense staining on the cell bodies, neuorpil threads and dystrophic neurites throughout the nucleus but no amyloid staining in the neighborhood. So this pathology seems to start without any amyloid. Alz-50 staining is often seen as the start of cell death, a sign that cells are slowing down their metabolism and that they will soon die. If one counts the number of cells in this nucleus - and this another advantage of this area in that the nuclei can be delineated very well so you can do total cell counts - you can see that during normal aging there is very little loss of cells (graph unavailable). The controls and the Alzheimer patients show the same cell number. This shows that although there is a tremendous staining with Alz-50, there is no cell death, yet in other disease processes like Huntington's disease there is a tremendous neuronal death in this nucleus. So the cells are primed to die in another disease process but not in Alzheimer's disease although there is a very dense staining of Alz-50. This holds for other areas as well. There are areas where there is no amyloid and yet there is Alz-50 staining, like the suprachiasmatic nucleus. There are areas where there is amyloid but no further Alzheimer's changes, the cerebellum for instance. There are areas where there are no senile plaques, etcetera.