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.
Similar content being viewed by others
References
Bertrand P., Roger O., Houlgatte R., Javoy-Agid F., Brandel J. P., Doble A., and Blanchard J. C. (1992) Measurement of nerve growth factor-like immunoreactivity in the human brain using an anti-mouse-NGF enzyme immunoassay.Neurochem. Int.,20, 215–218.
Boissiere F., Hunot S., Faucheux B., Mouatt-Prigent A., Agid Y., and Hirsch E. C. (1994) High affinity neurotrophin receptors in cholinergic neurons in the human brain.C. R. Acad. Sci. Paris, Sci. de la vie/Life Sci. 318, 997–1003.
Brandel J. P., Hirsch E., Malessa S., Duyckaerts C., Cervera P., and Agid Y. (1991) Differential vulnerability of cholinergic projections to the mediodorsal nucleus of the thalamus in senile dementia of Alzheimer type and progressive supranuclear palsy.Neuroscience 41, 25–31.
Dreyfus C. F. (1989) Effects of nerve growth factor on cholinergic brain neurons.Trends Pharmacol. 10, 145–149.
Ernfors P., Lindefors N., Chan-Palay V., and Persson H. (1990) Cholinergic neurons of the nucleus basalis express elevated levels of nerve growth factor receptor mRNA in senile dementia of the Alzheimer's type.Dementia 1, 138–145.
Goedert M., Fine A., Hunt S. P., and Ullrich A. (1986) Nerve growth factor mRNA in the peripheral and central rat tissues and in human central nervous system: lesion effects in the rat brain and levels in Alzheimer's disease.Mol. Brain Res. 1, 85–92.
Goedert M., Fine A., Dawbarn D., Wilcock G. K., and Chao M. V. (1989) Nerve growth factor receptor mRNA distribution in human brain: normal levels in basal forebrain in Alzheimer's disease.Mol. Brain. Res. 5, 1–7.
Hefti F. and Mash D. C. (1989) Localization of nerve growth factor receptors in the normal human brain and in Alzheimer's disease.Neurobiol. Aging 10, 75–87.
Ip N. Y., and Yancopoulos G. D. (1994) Neurotrophic factors and their receptors.Ann. Neurol. 35, S13-S16.
Lehéricy S., Hirsch E. C., Cervera P., Hersh L. B., Hauw J. J., Ruberg M., and Agid Y. (1989) Selective loss of cholinergic neurons in the ventral striatum of patients with Alzheimer's disease.Proc. Natl. Acad. Sci. USA 86, 8580–8584.
Lehéricy S., Hirsch E. C., Cervera-Piérot P., Hersh L. B., Bakchine S., Piette F., Duyckaerts C., Hauw J. J., Javoy-Agid F. and Agid Y. (1993) Heterogeneity and selectivity of the degeneration of cholinergic neurons in the basal forebrain of patients with Alzheimer's disease.J. Comp. Neurol 330, 15–31.
Mufson E. J., Bothwell M., Hersh L. B., and Kordower H. J. (1989a) Nerve growth factor receptor in the normal, aged human basal forebrain: colocalization with cholinergic neurons.J. Comp. Neurol. 285, 196–217.
Mufson E. J., Bothwell M., and Kordower J. H. (1989b) Loss of nerve growth factor receptor-containing neurons in Alzheimer's disease: a quantitative analysis across subregions of the basal forebrain.Exp. Neurol. 105, 221–232.
Ruberg M., Mayo W., Brice A., Duyckaerts C., Hauw J. J., Simon, H., LeMoal M. and Agid Y. (1990) Choline acetyltransferase activity and3H vesamicol binding in the temporal cortex of patients with Alzheimer's disease, Parkinson's disease, and rats with basal forebrain lesions.Neuroscience,35, 327–333.
Strada O., Hirsch E. C., Javoy-Agid F., Lehéricy S., Ruberg M., Hauw J. J., and Agid Y. (1992a) Does loss of Nerve Growth Factor Receptors precede loss of cholinergic neurons in Alzheimer's disease? An autoradiographic study in the human striatum and basal forebrain.J. Neurosci. 12, 4766–4774.
Strada O., Vyas S., Hirsch E. C., Ruberg M., Brice A., Agid Y., and Javoy-Agid F. (1992b) Decreased choline acetyltranferase mRNA expression in the nucleus basalis of Meynert in Alzheimer's disease: anin situ hybridization study.Proc. Natl. Acad. Sci. USA 89, 9549–9553.
Woolf N. J., Gould E. and Butcher L. L. (1989) Nerve growth factor receptor is associated with cholinergic neurons of the basal forebrain but not the pontomesencephalon.Neuroscience 30, 143–152.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Boissière, F., Lehéricy, S., Strada, O. et al. Neurotrophin receptors and selective loss of cholinergic neurons in Alzheimer disease. Molecular and Chemical Neuropathology 28, 219–223 (1996). https://doi.org/10.1007/BF02815225
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF02815225