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Well if activity is so important for the clinical symptoms, then it must also be possible to reactivate the neurons and have the clinical symptoms disappear. Well this of course is a dream, but there is a little bit of evidence for this approach in Alzheimer's disease. This is not directed towards the prevention of cell death but is directed towards the reactivation of neurons which are still there but don't function any longer.

In our lab, we developed an apparatus to monitor the suprachiasmatic nucleus, the clock of the brain. It is kind of a watch which one can carry and monitor your own activity day to night to day . It has a nice 24-hour rhythm. In an Alzheimer patient there are quiet periods but they occur at non-selective moments. The clear circadian rhythm had disappeared, there is no 24-hour rhythm coming over the line of significance. This helps explain why Alzheimer patients are so restless during the night. They lack the normal circadian pattern. This is the main reason that patients are brought into a home because the partner cannot take care of a patient day and night.

If you count the number of vasopressin cells in the suprachiasmatic nucleus you see that at a more advanced age there is a drop in cell number in the cells expressing vasopressin which is not the same as a drop in cell number. If you compare the Alzheimer's patient to age-matched controls (60-80 yrs), the Alzheimer patients only have one fourth of the number of vasopressin expressing cells. One must remember vasopressin is one of the main transmitters in the suprachiasmatic nucleus. This nucleus can easily be stimulated by light because it has a direct input from the optic nerve into the nucleus. That means that if you give Alzheimer's patients light for a few hours a day, extra light, then one stimulates the suprachiasmatic nucleus. One finds that the circadian rhythm improves and restlessness decreases. This is an interesting picture for many reasons, because it also shows the difference between Japan and the Netherlands because if you tell an Alzheimer patient in the Netherlands to sit in front of a light source, they wouldn't listen and they wouldn't do it. In Japan, they just do it. In Amsterdam we have a whole room of extra light and you see the same in patients; circadian rhythm comes back and restlessness decreases. Well this doesn't cure Alzheimer's disease, but it shows that in principle there is still plasticity in an area that is affected. If you stain for the suprachiasmatic nucleus by means of Alz-50 you see neuropil threads, you see accumulation of Alz-50 in the cell body so the area is clearly affected by the Alzheimer process but yet if you stimulate neurons you can clearly get function back.