Dick Swaab and Ahmad Salehi
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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
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.