Burke W J, Chung H D, Huang J S, Huang S S, Haring J H, Strong R, Marshall G L, Joh T H
Department of Neurology, Veterans Administration Medical Center, St Louis, MO.
Ann Neurol. 1988 Oct;24(4):532-6. doi: 10.1002/ana.410240409.
Alzheimer's disease (AD) is associated with a progressive loss of locus ceruleus neurons. These noradrenergic neurons receive a major afferent projection from epinephrine neurons in epinephrine cell groups in the brainstem. The epinephrine neurons have a specific enzymatic marker, phenylethanolamine N-methyltransferase (PNMT), which allows them to be identified chemically and immunohistochemically. We have previously reported a decrease in PNMT in brains of patients with AD. We now report that the decrease in PNMT activity in projections to the locus ceruleus is not due to the loss of epinephrine neurons, although up to 33% of these neurons are atrophic. The decrease in presynaptic PNMT does, however, correlate with the loss of postsynaptic locus ceruleus neurons in brains from AD patients. The percentage of degenerating neurons in the epinephrine nuclei also correlates significantly with the amount of loss of locus ceruleus neurons in AD. In addition, there is a 55% decrease in mitogen activity, a nonspecific measure of growth or maintenance factors, in dialysed locus ceruleus extracts from the AD patients compared to those from control subjects. The mitogen activity in the locus ceruleus was significantly correlated with PNMT activity and with the density of locus ceruleus neurons in all cases examined. These findings provide evidence for the hypothesis that retrograde degeneration is a mechanism of neuronal degeneration in AD and suggest that trophic factors may play a role in this process.
阿尔茨海默病（AD）与蓝斑神经元的进行性丧失有关。这些去甲肾上腺素能神经元接受来自脑干肾上腺素细胞群中肾上腺素能神经元的主要传入投射。肾上腺素能神经元具有一种特异性酶标记物，苯乙醇胺N - 甲基转移酶（PNMT），这使得它们能够通过化学和免疫组织化学方法被识别。我们之前报道过AD患者大脑中PNMT减少。我们现在报告，尽管高达33%的这些神经元萎缩，但投射到蓝斑的PNMT活性降低并非由于肾上腺素能神经元的丧失。然而，突触前PNMT的减少确实与AD患者大脑中突触后蓝斑神经元的丧失相关。肾上腺素核中退化神经元的百分比也与AD中蓝斑神经元的丧失量显著相关。此外，与对照组相比，AD患者透析后的蓝斑提取物中促有丝分裂活性降低了55%，促有丝分裂活性是生长或维持因子的一种非特异性测量指标。在所有检测的病例中，蓝斑中的促有丝分裂活性与PNMT活性以及蓝斑神经元密度显著相关。这些发现为逆行性变性是AD中神经元变性的一种机制这一假说提供了证据，并表明营养因子可能在这一过程中起作用。
