Neurotrophin receptors and selective loss of cholinergic neurons in Alzheimer disease |
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Institution: | (1) Laboratoire de Médecine Expérimentale, Physiologie et Pathogénèse des Maladies Dégénératives du Système Nerveux, INSERM U289, H?pital de la Salpêtrière, 47 Boulevarde l'H?pital, 75013 Paris, France |
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Abstract: | The most consistent neuropathological finding in Alzheimer disease (AD) is the loss of cholinergic neurons of the nucleus
basalis of Meynert (NbM). Using immunohistochemistry, we have previously shown that cholinergic neurons located in the ventral
striatum were affected, whereas those of the caudate nucleus, putamen, and mesencephalon were spared. Since cholinergic neurons
that degenerate in AD are sensitive to NGF and those that are spared are not, it has been hypothesized that the loss of neurotrophins
receptors may play a role in the death of cholinergic neuronsin AD. Using immunohistochemistry, we have detected the presence
of TrkA on most cholinergic neurons from the NbM, on some from those of the striatum, but not on those of the mesencephalon
in the human brain. In AD patients, the number of neurons that expressed TrkA was markedly decreased in the NbM very likely
as a consequence of cholinergic neuronal loss. In the striatum, despite the loss of high-affinity NGF binding prevously reported,
no loss of TrkA was observed. Taken together, these results suggest a decreased expression of NGF receptors on the striatal
cholinergic neurons in AD. This loss may contribute, when it reaches a crucial threshold, to the death of cholinergic neurons
occurring in AD. |
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Keywords: | Alzheimer disease choline acetyltransferase nerve growth factor neurotrophin receptors striatum nucleus basalis of Meynert |
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