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The other side of the coin is that in those areas in which we don't see any Alzheimer changes -- and there are some areas of the brain that seem very resistant to the Alzheimer process --we find a very high metabolic activity. A good example of that is the paraventricular nucleus and the supraoptic [nucleus] which don't show any Alzheimer's changes. You can see staining for the Golgi apparatus in a young control patient, and again around the nucleus you can see the black Golgi staining, but in an aged individual, normal aged individual, the Golgi apparatus is much larger. Those neurons are activated in the course of aging from the age of forty onward. This hold true for the vasopressin cells also probably because the kidney is losing receptors for vasopressin so the brain has to produce more vasopressin in order to keep water metabolism intact. It also holds for the CRH neurons that are activated form the age of forty onward. The oxytocin neurons remain stable. The idea that in those areas where a high metabolic rate is found you also find resistance to Alzheimer's changes has been paraphrased by us as "use it of loose it".

Well, if there is a relationship between Alzheimer's changes and metabolism then the next question is: do the Alzheimer changes cause a decrease in neuronal metabolism? Well the decreased metabolism is not due to Alz-50 and I'll show that it is not due to the presence of plaques or tangles either. It's not due to Alz-50 because in the nucleus tuberalis lateralis the metabolic rate remains stable although the cells are loaded with Alz 50.

In order to study the relationship between plaques and tangles we studied the CA area. What we did was first stain to determine the size of the Golgi apparatus in a number of neurons in the area, then we did a Bodian's stain as can be seen here. You can see the tangles and the plaques and we combined these measurements by image analysis techniques. First, CA1 is clearly an area where metabolic rate is decreased. You see the slide of the Golgi apparatus is going down from 30 to 20 in Alzheimer patients as compared to controls. No doubt about the decreased metabolism in that area. However, the interesting thing is that everyone presumes that a tangle is bad for the metabolic rate in a neuron but this seems not to be true. If one compares a neuron which contains a tangle with a neurons that do not contain a tangle and one measures the Golgi apparatus one finds there is no difference. This also means that these two changes, change in the metabolic rate and presence of a tangle, seem in principle to be independent.