Neurotrophin receptors and selective loss of cholinergic neurons in Alzheimer disease.
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 neurons in 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 previously 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.
Boissière
F
F
Laboratoire de Médecine Expérimentale, Physiologie et Pathogénèse, Maladies Dégénératives du Système Nerveux, INSERM U289, Hôpital de la Salpêtrière, Paris, France.
Lehéricy
S
S
Strada
O
O
Agid
Y
Y
Hirsch
E C
EC
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D006801:Humans; D009410:Nerve Degeneration; D009414:Nerve Growth Factors / Q000378:metabolism / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D009928:Organ Specificity; D011518:Proto-Oncogene Proteins / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000032:analysis / Q000378:metabolism*
D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D017475:Receptors, Nerve Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA