Trk neurotrophin receptors in cholinergic neurons of patients withAlzheimer's disease
F. Boissiere
Bok Engelsk 1997
| Utgitt | 1997
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| Omfang | Side 1- 8
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| Opplysninger | Besides cortical pathology, Alzheimer's disease (AD) is characterizedby a loss of cholinergic neurons in the basal forebrain but not inthe caudate nucleus, putamen or mesencephalon. Since cholinergicneurons which degenerate in AD are sensitive to nerve growth factor(NGF), a link between NGF sensitivity and the vulnerability ofcholinergic neurons has been suspected. Levels of NGF are not alteredin patients with AD, however. Thus, cholinergic nerve cell death inAD could result from a deficiency in NGF receptors. Using sequentialimmunohistochemistry with antibodies that recognize preferentiallyTrkA, the specific receptor for NGF, and with antibodies directedagainst choline acetyltransferase we analyzed the expression ofneurotrophin receptors in cholinergic neurons from control and ADbrains. TrkA was expressed on cholinergic neurons of the striatum andnucleus basalis of Meynert but not on those of the mesencephalon. InAD patients, the number of neurons expressing TrkA was markedlydecreased in the nucleus basalis of Meynert, very likely as aconsequence of cholinergic neuronal loss. No loss of TrkA-positiveneurons was observed in the striatum. Taken in conjunction with ourpreviously published report of loss of high-affinity NGF binding inthe striatum of AD patients, our results suggest a reduced expressionof TrkA, the specific receptor for NGF, on striatal cholinergicneurons in AD. The loss of neurotrophin receptors may contribute tothe alteration of cholinergic neurons occurring in AD.
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| Emner |
