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In my opinion, metabolic decrease is one of the main hallmarks of Alzheimer's disease. What then may cause this metabolic decrease? We think that the high-affinity receptors for neurotrophins might be a key factor in this.

In a control subject, the high-affinity Trk-A receptor is present in the cell bodies of the nucleus basalis of Mynert. In Alzheimer's patients you can see the cell but no Trk-A receptors are present anymore in the cell bodies. This means that the main transport mechanism for neurotrophins which are collected from the cortical areas by those cells is lacking in Alzheimer's disease. In Alzheimer's patients, the percentage of cells which contain Trk A, B or C, three types of high-affinity neurotrophin receptors, is very strongly decreased in all three types. It is the number of cells containing this high-affinity receptor, Trk-A, that is affected most clearly.

This gives an alternative hypothesis to the pathogenesis of Alzheimer's disease, which we see as a multifactorial disease. Many factors might cause it probably on the basis of the aging process, an acceleration of the process such that dementia results. But the signs that we know so well from neuropathology have to be considered as independent of the dementia. Atrophy--inactivity of neurons--is in my opinion much more important. Of course there are also protective factors which seem to be different in different brain areas but in general they have to do something with activation. Whereas those factors which cause an acceleration of the process, like ApoE 4, cause decreased activity in neurons.