Palmer A M, DeKosky S T
Department of Psychiatry, Western Psychiatric Institute, PA.
J Neural Transm Gen Sect. 1993;91(2-3):135-59. doi: 10.1007/BF01245229.
The integrity of dopaminergic, noradrenergic and serotonergic neurons in normal aging and Alzheimer's disease is reviewed. Loss of dopaminergic innervation of the neostriatum is a prominent age-related change, which corresponds with the age-related loss of dopaminergic cell bodies from the substantia nigra. This change is regionally specific, since dopaminergic innervation of the neocortex and the neostriatum are not affected. Although there is an age-related loss of noradrenergic cell bodies from the locus coeruleus, most studies indicate normal concentrations of noradrenaline in target areas. There is also evidence for reduced serotonergic innervation of the neocortex and, less convincingly, the neostriatum. Alzheimer's disease is associated with more pronounced noradrenergic and serotonergic denervation but, unlike normal aging, dopaminergic innervation of neostriatum is intact; although dopamine neurons are probably dysfunctional in this region. Studies relating neuronal markers to the symptomatology of Alzheimer's disease indicate that dysfunction of monoamine neurons is more closely linked to non-cognitive than to cognitive changes in behavior. In addition, monoaminergic therapies have been successful in ameliorating affective and psychotic behaviors along with sleep disturbances in both Alzheimer's disease and senescence. It seems likely that monoaminergic therapies (developed as we learn more about alterations in dopamine, noradrenaline and serotonin) will continue to be necessary to treat such behavioral disturbances.
本文综述了正常衰老和阿尔茨海默病中多巴胺能、去甲肾上腺素能和5-羟色胺能神经元的完整性。新纹状体多巴胺能神经支配的丧失是一种与年龄相关的显著变化，这与黑质中多巴胺能细胞体随年龄增长而减少相对应。这种变化具有区域特异性，因为新皮质和新纹状体的多巴胺能神经支配不受影响。尽管蓝斑中去甲肾上腺素能细胞体随年龄增长而减少，但大多数研究表明，靶区域中去甲肾上腺素浓度正常。也有证据表明新皮质的5-羟色胺能神经支配减少，而新纹状体的减少则不太令人信服。阿尔茨海默病与更明显的去甲肾上腺素能和5-羟色胺能去神经支配有关，但与正常衰老不同，新纹状体的多巴胺能神经支配是完整的；尽管该区域的多巴胺神经元可能功能失调。将神经元标记物与阿尔茨海默病症状学相关联的研究表明，单胺能神经元功能障碍与行为中的非认知变化比与认知变化的联系更为紧密。此外，单胺能疗法已成功改善了阿尔茨海默病和衰老过程中的情感和精神行为以及睡眠障碍。随着我们对多巴胺、去甲肾上腺素和5-羟色胺变化了解的不断深入而开发的单胺能疗法，似乎仍将是治疗此类行为障碍所必需的。
