Boissière F, Hunot S, Faucheux B, Hersh L B, Agid Y, Hirsch E C
Laboratoire de Médecine Expérimentale, Physiopathologie et Pathogenèse des Maladies Dégénératives du Système Nerveux, INSERM U289, Hôpital de la Salpêtrière, Paris, France.
Dement Geriatr Cogn Disord. 1997 Jan-Feb;8(1):1-8. doi: 10.1159/000106594.
Besides cortical pathology, Alzheimer's disease (AD) is characterized by a loss of cholinergic neurons in the basal forebrain but not in the caudate nucleus, putamen or mesencephalon. Since cholinergic neurons which degenerate in AD are sensitive to nerve growth factor (NGF), a link between NGF sensitivity and the vulnerability of cholinergic neurons has been suspected. Levels of NGF are not altered in patients with AD, however. Thus, cholinergic nerve cell death in AD could not result from a deficiency in NGF receptors. Using sequential immunohistochemistry with antibodies that recognize preferentially TrkA, the specific receptor for NGF, and with antibodies directed against choline acetyltransferase we analyzed the expression of neurotrophin receptors in cholinergic neurons from control and AD brains. TrkA was expressed on cholinergic neurons of the striatum and nucleus basalis of Meynert but not on those of the mesencephalon. In AD patients, the number of neurons expressing TrkA was markedly decreased in the nucleus basalis of Meynert, very likely as a consequence of cholinergic neuronal loss. No loss of TrkA-positive neurons was observed in the striatum. Taken in conjunction with our previously published report of loss of high-affinity NGF binding in the striatum of AD patients, our results suggest a reduced expression of TrkA, the specific receptor for NGF, on striatal cholinergic neurons in AD. The loss of neurotrophin receptors may contribute to the alteration of cholinergic neurons occurring in AD.
除了皮质病变外，阿尔茨海默病（AD）的特征还在于基底前脑胆碱能神经元的丧失，而尾状核、壳核或中脑的胆碱能神经元则未丧失。由于在AD中退化的胆碱能神经元对神经生长因子（NGF）敏感，因此人们怀疑NGF敏感性与胆碱能神经元的易损性之间存在联系。然而，AD患者的NGF水平并未改变。因此，AD中胆碱能神经细胞死亡并非由NGF受体缺乏所致。我们使用能优先识别NGF特异性受体TrkA的抗体以及针对胆碱乙酰转移酶的抗体进行连续免疫组织化学，分析了对照和AD脑胆碱能神经元中神经营养因子受体的表达。TrkA在纹状体和迈内特基底核的胆碱能神经元上表达，但在中脑的胆碱能神经元上不表达。在AD患者中，迈内特基底核中表达TrkA的神经元数量明显减少，这很可能是胆碱能神经元丧失的结果。在纹状体中未观察到TrkA阳性神经元的丧失。结合我们之前发表的关于AD患者纹状体中高亲和力NGF结合丧失的报告，我们的结果表明，AD中纹状体胆碱能神经元上NGF的特异性受体TrkA表达减少。神经营养因子受体的丧失可能导致AD中胆碱能神经元的改变。
